Affinage

CD52

CAMPATH-1 antigen · UniProt P31358

Length
61 aa
Mass
6.6 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD52 (CAMPATH-1/CDw52) is a GPI-anchored cell-surface glycoprotein with an exceptionally short mature peptide of only 12-18 amino acids carrying a single N-linked oligosaccharide at Asn3, expressed on lymphocytes and other immune cells as well as in the male reproductive tract (PMID:1711975, PMID:8418821). Its proximity to the membrane and GPI anchor make it an efficient target for complement-mediated lysis, the basis for the therapeutic antibody alemtuzumab whose in vivo depleting activity is mediated principally by FcγR-bearing neutrophils, NK cells, and macrophages rather than complement (PMID:8366859, PMID:14559836, PMID:19740383). On the lymphocyte surface CD52 self-associates and physically couples to the TCR, transducing tyrosine-kinase signals through p56lck/p59fyn in a manner dependent on co-expression of the TCR and the CD45 phosphatase (PMID:10744652). CD52 functions as a homeostatic inhibitory molecule: a soluble form released from activated T and B cells by phospholipase C-mediated shedding suppresses lymphocyte activation, requiring tetra-antennary α-2,3-sialylated N-glycans for bioactivity (PMID:23685786, PMID:31507595, PMID:33658999). Mechanistically, soluble CD52 binds the proinflammatory Box B domain of the DAMP protein HMGB1 via its sialylated glycan, which promotes engagement of the inhibitory receptor Siglec-10, triggering Siglec-10 phosphorylation and recruitment of the SHP1 phosphatase to its ITIM, thereby impairing Lck/Zap70 phosphorylation (PMID:29997173). CD52 broadly dampens innate inflammatory signaling, inhibiting TLR/TNFR-driven NF-κB activation and, at high concentrations, depleting MCL-1 to activate BAX/BAK-dependent intrinsic apoptosis, with CD52-knockout mice showing exacerbated LPS responses (PMID:29244050). CD52 also exerts inhibitory effects on eosinophil reactive oxygen species production, monocyte adhesion, and B-cell receptor signaling, and its expression is regulated by cytokines (IL-4/IL-13 via STAT6; IFN/LPS via JAK1/HDAC IIa) and RAS signaling (PMID:8977262, PMID:33760395, PMID:24760752). In the male genital tract CD52 is acquired by maturing spermatozoa during epididymal transit and carries distinct, PLC-resistant palmitoylated GPI anchors and complex N-glycans, but it is dispensable for fertility in the mouse (PMID:7685389, PMID:10514467, PMID:18782223).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    Establishing CD52 as a GPI-anchored glycoprotein with a uniquely minimal peptide backbone defined the molecular nature of the CAMPATH-1 antigen and explained its accessibility at the cell surface.

    Evidence Protein purification, N-terminal sequencing, cDNA cloning, and PLC treatment

    PMID:1711975

    Open questions at the time
    • No endogenous physiological ligand identified at this stage
    • Function of the short peptide unknown
  2. 1993 High

    Localizing the antibody epitope to the C-terminal GPI-proximal region explained why CD52 is an efficient target for complement lysis, and reconstitution showed the antigen can be transferred onto cells to confer sensitivity.

    Evidence Complement lysis assay, antigen reincorporation, proteolytic and deglycosylation manipulations

    PMID:8366859

    Open questions at the time
    • Did not address signaling or non-antibody-dependent function
    • Effector mechanism in vivo not tested
  3. 1993 High

    Identification of the epididymal HE5 gene as encoding the same backbone as lymphocyte CDw52 established that a single-copy gene produces CD52 in both immune and male reproductive tissues, while sperm functional assays raised a reproductive role.

    Evidence Differential cDNA screening, in situ hybridization, Southern blot, sperm motility assay with complement

    PMID:7685389 PMID:8418821

    Open questions at the time
    • Causal requirement of CD52 in sperm function not established
    • Tissue-specific modifications not yet characterized
  4. 1995 Medium

    Demonstrating that anti-CD52 cross-linking drives T-cell proliferation and lymphokine production in a cyclosporin-sensitive manner first implicated CD52 as a costimulatory signaling molecule rather than an inert antigen.

    Evidence Primary T-cell proliferation and lymphokine assays with cyclosporin A inhibition and antibody co-immobilization

    PMID:7718516

    Open questions at the time
    • Molecular signaling intermediates not defined
    • Reliance on antibody cross-linking rather than a natural ligand
  5. 1996 High

    Extending CD52 expression and inhibitory function to eosinophils showed it can dampen innate effector responses, broadening its role beyond lymphocytes.

    Evidence Flow cytometry, PLC treatment, and reactive oxygen species assays with multiple stimuli

    PMID:8977262

    Open questions at the time
    • Signaling pathway for ROS inhibition not mapped
    • Endogenous trigger unknown
  6. 1997 Medium

    Tracking CD52 acquisition across epididymal regions and identifying PLC-resistant palmitoylated GPI anchors revealed tissue-specific post-translational tailoring of the molecule during sperm maturation.

    Evidence Quantitative flow cytometry across epididymal regions; PLC treatment, filtration of seminal plasma

    PMID:9291477 PMID:9464849

    Open questions at the time
    • Correlation with motility not shown to be causal
    • Carrier identity in seminal plasma undefined
  7. 1998 Medium

    Showing that anti-CD52 cross-linking induces Fas-independent apoptosis in lymphoid lines, accompanied by loss of GPI biosynthesis, illuminated antibody-induced cell death and a route to antigen-loss escape.

    Evidence Cell growth and apoptosis assays, flow cytometry, in vivo xenograft reversal

    PMID:9824507

    Open questions at the time
    • Mechanism linking cross-linking to GPI synthesis defect unclear
    • Relevance to physiological signaling uncertain
  8. 1998 High

    Crystal structures of the rat and humanized CAMPATH Fab fragments defined the antibody-combining site and the framework determinants of humanization, supporting therapeutic antibody engineering.

    Evidence X-ray crystallography of CAMPATH-1G and CAMPATH-1H Fab fragments

    PMID:9811544

    Open questions at the time
    • Structure of the antigen-bound complex not resolved here
    • No insight into CD52 native function
  9. 2000 High

    Demonstrating that CD52 signaling requires both TCR and CD45 and triggers lck/fyn-dependent phosphorylation, with FRET-confirmed CD52 homo-association and CD52-TCR coupling, defined the membrane signaling architecture of surface CD52.

    Evidence Tyrosine phosphorylation assays in transfected Jurkat subclones, FRET, pharmacological inhibition

    PMID:10744652

    Open questions at the time
    • Downstream transcriptional consequences not mapped
    • Molecular basis of CD52-TCR association undefined
  10. 2003 Medium

    FcRγ-knockout experiments established that alemtuzumab tumor killing in vivo depends on FcγR-bearing effector cells, redirecting the understanding of its mechanism away from pure complement lysis.

    Evidence NOD/SCID xenograft and FcRγ-knockout mouse survival analysis

    PMID:14559836

    Open questions at the time
    • Relative contribution of ADCC versus apoptosis not quantified
    • Single tumor model
  11. 2009 High

    Using human CD52 transgenic mice, depletion was shown to be complement-independent and mediated by neutrophils and NK cells, refining the in vivo effector requirements of alemtuzumab.

    Evidence Transgenic model, cobra venom factor complement depletion, antibody depletion of Gr-1+ and asialo-GM-1+ cells

    PMID:19740383

    Open questions at the time
    • Human-specific effector contributions may differ
    • Does not address antigen biology
  12. 2013 High

    Identifying soluble CD52 released by PLC as a Siglec-10-binding suppressor of Lck/Zap70 phosphorylation, with CD52hi depletion accelerating diabetes, established CD52 as a regulatory immunosuppressive mediator.

    Evidence PLC release assay, Siglec-10 binding, kinase phosphorylation assays, NOD mouse adoptive transfer

    PMID:23685786

    Open questions at the time
    • Direct vs indirect Siglec-10 binding not yet resolved
    • Glycan dependence not yet defined
  13. 2017 High

    Demonstrating that soluble CD52 inhibits TLR/TNFR-driven NF-κB activation and triggers MCL-1-depletion/BAX-BAK apoptosis at high doses, with CD52-knockout exacerbating LPS responses, defined a broad innate-immune anti-inflammatory role.

    Evidence NF-κB reporters, cytokine measurement, MCL-1/BAX/BAK assays, CD52 knockout mice, LPS shock model

    PMID:29244050

    Open questions at the time
    • Receptor mediating innate NF-κB inhibition not fully resolved
    • Concentration thresholds in vivo unclear
  14. 2018 High

    Resolving HMGB1 as a glycan-dependent intermediary that bridges soluble CD52 to Siglec-10, driving SHP1 recruitment to the Siglec-10 ITIM associated with the TCR, provided the complete mechanistic chain of CD52-mediated suppression.

    Evidence CD52-Fc binding, HMGB1 domain-specific blocking, multi-protein co-IP, Siglec-10 phosphorylation assays

    PMID:29997173

    Open questions at the time
    • Stoichiometry of the CD52/HMGB1/Siglec-10 complex undefined
    • In vivo requirement of HMGB1 not tested
  15. 2019 High

    Showing that bioactivity strictly requires tetra-antennary α-2,3-sialylated N-glycans, with loss and enzymatic restoration of function, established the glycan code underlying CD52 immunosuppression.

    Evidence Glycomic mass spectrometry, enzymatic desialylation/re-sialylation, T-cell suppression bioassay

    PMID:31507595

    Open questions at the time
    • Glycosyltransferases producing bioactive glycoform in vivo unidentified
    • Role of O-glycans at Ser12 not functionally isolated
  16. 2021 Medium

    Extending the inhibitory model to B cells and monocytes showed CD52 restrains BCR signaling (partly via Siglec-10) and monocyte adhesion, and identified IL-4/IL-13-STAT6 and IFN/LPS-JAK1/HDAC IIa as regulators of its expression.

    Evidence CD52-knockout JeKo-1 cells, BCR signaling and adhesion assays, recombinant CD52-Fc, pathway inhibitors

    PMID:33658999 PMID:33760395

    Open questions at the time
    • Whether the same HMGB1/Siglec-10 axis operates in B cells and monocytes not fully established
    • Adhesion mechanism (CD18 regulation) not molecularly traced
  17. 2024 Medium

    Demonstrating that CLL-derived CD52 suppresses CAR T-cell function via Siglec-10, reversible by CD40/SRC-mediated downregulation, extended the inhibitory axis to a tumor immune-evasion mechanism with therapeutic implications.

    Evidence CLL/CAR T co-culture, CD52/CD24 antibody blocking, dasatinib inhibition, transcriptome profiling

    PMID:39042920

    Open questions at the time
    • Relative contribution of CD52 versus CD24 not isolated
    • Single-lab co-culture system

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous receptor(s) and signaling mechanism mediating surface CD52 costimulation, the physiological trigger and in vivo relevance of the HMGB1/Siglec-10 suppressive axis across cell types, and the in vivo enzymes generating bioactive glycoforms remain to be integrated into a single model.
  • No structure of native CD52 bound to HMGB1 or Siglec-10
  • Reconciliation of costimulatory surface signaling with inhibitory soluble signaling unresolved
  • Physiological function of reproductive-tract CD52 unknown given fertility of knockout mice

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CD45HMGB1LCKPTPN6SIGLEC10TCR

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CD52 (CAMPATH-1/CDw52) is a GPI-anchored glycoprotein with an exceptionally short mature peptide of 12–18 amino acid residues and a single N-linked oligosaccharide at Asn3. The antigenic epitope is heat-stable but sensitive to mild alkali, and the protein is anchored by a glycosylphosphatidylinositol (GPI) anchor as demonstrated by phosphatidylinositol-specific phospholipase C treatment. Protein purification, N-terminal sequencing, PCR-based cDNA cloning, phospholipase C treatment European journal of immunology High 1711975
1993 The antigenic epitope of CD52 recognized by CAMPATH-1 antibodies resides in a proteolytic fragment containing the C-terminal tripeptide and the GPI anchor; proximity of the epitope to the cell membrane (not the N-linked sugar or the first nine amino acids) is the key feature making it an efficient target for complement-mediated lysis. Both native and deglycosylated antigen, as well as proteolytic fragments, can be reincorporated into target cells to confer complement sensitivity. Complement lysis assay, antigen reincorporation into cells, proteolytic fragmentation, deglycosylation Molecular immunology High 8366859
1993 CD52 (CDw52/HE5) is expressed at high levels in the male reproductive system (epididymis, seminal vesicle, seminal plasma) and is acquired by maturing (but not testicular) spermatozoa during epididymal transit, representing a novel mechanism of cell-surface antigen acquisition. In the presence of human complement, CAMPATH-1 antibodies inhibit sperm motility; seminal plasma blocks antibody binding and protects sperm. Immunohistochemistry, flow cytometry, sperm motility assay with complement Journal of reproductive immunology Medium 7685389
1993 The human epididymal gene HE5 encodes the same peptide backbone as the lymphocyte differentiation antigen CDw52 (CD52); both products are transcribed from a single-copy gene, and expression is highly restricted to epithelial cells of the epididymal and deferent duct. Differential cDNA library screening, sequencing, Northern blot, in situ hybridization, Southern blot Molecular reproduction and development High 8418821
1995 Cross-linking of CD52 on normal resting CD4+ and CD8+ T lymphocytes with anti-CD52 antibodies induces proliferation and lymphokine production in the presence of phorbol esters (or directly with one antibody), and augments anti-CD3-mediated responses when co-immobilized; this activation is inhibited by cyclosporin A, implicating calcineurin-dependent signal transduction pathways. Anti-CD52 antibodies did not synergize with anti-CD2 or anti-CD28, and did not inhibit antigen-specific T cell responses. T cell proliferation assay, lymphokine production assay, cyclosporin A inhibition, co-immobilization of antibodies International immunology Medium 7718516
1996 CD52 is expressed on the surface of human eosinophils (but not neutrophils) as a GPI-anchored molecule (confirmed by phospholipase C treatment). Cross-linking of CD52 on eosinophils dose-dependently inhibits reactive oxygen species production stimulated by C5a, platelet-activating factor, and GM-CSF, identifying a functional inhibitory role for CD52 on eosinophils. Flow cytometry, RT-PCR, Northern blot, phospholipase C treatment, reactive oxygen species assay Blood High 8977262
1998 Cross-linking CD52 on B-cell and Jurkat T-cell lines (but not receptor-mediated stimulation) induces growth inhibition and apoptosis (Fas/FasL-independent pathway in Wien 133 B cells). Cells surviving anti-CD52 treatment down-regulate CD52 and other GPI-anchored molecules (CD59, CD55) but not transmembrane molecules, due to a defect in GPI precursor synthesis; this phenotype is reversible in vitro and in vivo. Cell growth assay, flow cytometry, apoptosis assay, in vivo mouse xenograft Immunology Medium 9824507
1999 Male genital tract CD52 differs structurally from lymphocyte CD52: the sperm/seminal plasma form carries mostly 2-inositol palmitoylated, alkylacylglycerol GPI anchors (rendering it resistant to phospholipase C) and highly charged, complex-type N-glycans with lactosamine repeats and peripheral fucose, distinct from the lymphocyte form. Protein purification from seminal plasma, Western blot, structural mass spectrometry of glycans and GPI anchor The Journal of biological chemistry High 10514467
2000 CD52-mediated signal transduction in T cells requires the co-expression of both the T cell receptor (TCR) and the CD45 tyrosine phosphatase at the cell surface; cross-linking of CD52 triggers TCR-dependent protein tyrosine phosphorylation (involving p56lck and p59fyn regulated by CD45) without activating phospholipase Cγ1 or calcium signals. FRET analysis demonstrated CD52 homo-association at the cell surface independent of TCR/CD45, and CD52-TCR association in CD45+TCR+ cells. Protein tyrosine phosphorylation assay in primary T cells and Jurkat subclones transfected with CD52, FRET, pharmacological inhibition International immunology High 10744652
2003 In a murine ATL model, the major tumor-killing mechanism of alemtuzumab (anti-CD52) in vivo requires Fcγ receptor-containing receptors (e.g., FcγRIII) on polymorphonuclear leukocytes and macrophages, as demonstrated using FcRγ-knockout mice; FcRγ-mediated ADCC and/or cross-linking-induced apoptosis are the primary mechanisms. In vivo NOD/SCID mouse xenograft, FcRγ-knockout mice, survival analysis Cancer research Medium 14559836
2009 In a human CD52 transgenic mouse model, alemtuzumab-mediated lymphocyte depletion and cytokine induction are largely independent of complement (cobra venom factor treatment had no impact) but are mediated primarily by neutrophils and NK cells, as demonstrated by antibody depletion of Gr-1+ or asialo-GM-1+ populations. Transgenic mouse model, cobra venom factor complement depletion, antibody depletion of neutrophil (Gr-1) and NK cell (asialo-GM-1) populations, flow cytometry Immunology High 19740383
2013 Soluble CD52, released from the surface of activated T cells by phospholipase C, binds to the inhibitory receptor Siglec-10 on T cells and suppresses T cell activation by impairing phosphorylation of the TCR-associated kinases Lck and Zap70. Transfer of lymphocyte populations depleted of CD52hi cells into NOD mice substantially accelerated onset of diabetes. Phospholipase C release assay, Siglec-10 binding assay, kinase phosphorylation assay (Lck, Zap70), NOD mouse adoptive transfer Nature immunology High 23685786
2018 CD52-mediated suppression of T cells requires the DAMP protein HMGB1 as an intermediary: soluble CD52 binds specifically to the proinflammatory Box B domain of HMGB1 via its N-linked glycan (α-2,3 sialic acid linkage with galactose), which then promotes binding to Siglec-10. This triggers tyrosine phosphorylation of Siglec-10 and recruitment of SHP1 phosphatase to the intracellular ITIM motif of Siglec-10, which associates with the TCR; T cell suppression was blocked by anti-HMGB1 antibody or Box A domain of HMGB1. CD52-Fc binding assays, HMGB1 domain-specific blocking, co-immunoprecipitation (CD52/HMGB1/Siglec-10/SHP1/TCR complex), Siglec-10 phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 29997173
2017 Soluble CD52 inhibits Toll-like receptor and TNF receptor signaling to limit NF-κB activation and reduce inflammatory cytokine production in macrophages, monocytes, and dendritic cells. At higher concentrations, soluble CD52 depletes MCL-1, activating BH3-only proteins BAX and BAK to cause intrinsic apoptotic cell death. In vivo, CD52 administration suppresses LPS-induced cytokine secretion, while genetic deletion of CD52 exacerbates LPS responses. NF-κB reporter assays, cytokine measurement, MCL-1/BAX/BAK protein assays, CD52 knockout mice, LPS endotoxic shock model Cell death and differentiation High 29244050
2019 CD52 bioactivity (T cell suppression) requires tetra-antennary α-2,3 sialylated N-glycans: removal of α-2,3 sialylation abolishes bioactivity, which is restored by re-sialylation with α-2,3 sialyltransferases. O-glycan core type-2 di-sialylated structures at Ser12 are also enriched in bioactive CD52 fractions. Glycomic analysis (porous graphitized carbon-ESI-MS/MS), glycopeptide analysis (C8-LC-ESI-MS), enzymatic desialylation and re-sialylation, anion exchange fractionation, T cell suppression bioassay Frontiers in immunology High 31507595
2021 On B cells, surface CD52 functions as a homeostatic inhibitory molecule: CD52-deficient JeKo-1 cells are hyperresponsive to BCR signaling. Antigen-specific BCR activation triggers CD52 cleavage in a phospholipase C-dependent manner, reducing surface CD52. Soluble CD52-Fc inhibits BCR signaling partially through Siglec-10, reduces surface immunoglobulin and CXCR5, and promotes expansion of IgD+IgMlo anergic B cells. CD52-knockout cell line (JeKo-1), BCR signaling assay, phospholipase C inhibition, recombinant CD52-Fc treatment, Siglec-10 blocking, flow cytometry Frontiers in immunology Medium 33658999
2021 In monocytes, CD52 expression negatively regulates cell adhesion: overexpression of CD52 decreases CD18 levels and monocyte adhesion, while knockdown of CD52 increases monocyte adhesion. CD52 expression is upregulated by IL-4/IL-13 via the STAT6 pathway and downregulated by LPS and type I/II IFNs via JAK1 and HDAC IIa. CD52 overexpression and siRNA knockdown in monocytes, adhesion assay, STAT6/JAK1/HDAC IIa pathway inhibitors, cytokine stimulation Arthritis & rheumatology (Hoboken, N.J.) Medium 33760395
1998 Crystal structures of the rat CAMPATH-1G and humanized CAMPATH-1H Fab fragments were solved at 2.6 Å and 3.25 Å resolution, revealing that the antibody-combining site is dominated by LysH52b and LysH53 protrusions from loop H2, and that framework residues H71 and H24 are major determinants of structural differences between rat and humanized antibody loops H1 and H2. X-ray crystallography Journal of molecular biology High 9811544
2019 Co-crystal structure of an anti-CD52 antibody Fab with a CD52 peptide mimetic solved at 2.2 Å (PDB 6OBD) revealed that Asn33 of the antibody light chain CDR1 directly contacts the CD52 phosphate group via a hydrogen bond; mutation of Asn33 to Asp (deamidation mimic) reduces antigen binding affinity ~400-fold. X-ray crystallography, site-directed mutagenesis, Biacore binding affinity measurement, CDC assay mAbs High 31199181
2008 CD52-null mice generated by gene disruption are fertile and show normal sperm viability, motility, morphology, and fertilizing ability both in vivo and in vitro, demonstrating that CD52 is not required for fertilization in the mouse despite being a major sperm maturation-associated antigen. Gene knockout (Cd52 null mice), in vitro fertilization, sperm parameter analysis, litter size measurement Genes to cells : devoted to molecular & cellular mechanisms High 18782223
1997 The GPI anchor of male genital tract CD52 contains 2-inositol palmitoylation that renders the molecule insensitive to phospholipase C cleavage, in contrast to lymphocyte CD52; sperm CD52 is acquired from epididymal secretions and associates with large molecular carriers in seminal plasma during transfer onto spermatozoa. Phospholipase C treatment, flow cytometry, Western blot, size filtration of seminal plasma Molecular reproduction and development Medium 9291477
2024 CLL cell-derived CD52 (and CD24) expressed on the CLL cell surface suppresses CAR T cell function via Siglec-10 signaling; blocking CD24 and/or CD52 markedly reduced CAR T cell dysfunction upon coculture with resting CLL cells. CD40 stimulation of CLL cells downregulated CD52 expression via SRC kinase signaling (reversed by dasatinib), restoring T cell function. Co-culture assays (CLL + CAR T cells), antibody blocking of CD52/CD24, dasatinib pharmacological inhibition, transcriptome profiling, flow cytometry Blood advances Medium 39042920
2005 Different glycoforms of CD52 associate differently with lipid microdomains: lymphocyte CD52 (both CAMPATH epitope and O-glycan-bearing glycoforms) resides in cholesterol-rich lipid rafts, whereas in capacitated sperm the O-glycoform associates with GM3-rich microdomains distinct from classical rafts. Heterologous CD52 insertion experiments confirmed the importance of the association between GM3 and O-glycans for specialized microdomain formation. Brij 98 solubilization, sucrose density gradient centrifugation, heterologous CD52 insertion (prostasomes into rat sperm), Western blot Biochemical and biophysical research communications Medium 16266689
2014 Activated RAS signaling profoundly promotes surface expression of CD52 on mast cells, as demonstrated in the MCPV-1 cell line generated by lentiviral immortalization. CD52 is expressed at high levels on neoplastic mast cells in advanced systemic mastocytosis but not on normal or indolent SM mast cells. Lentiviral immortalization, functional studies in MCPV-1 cell line, flow cytometry, NSG mouse xenograft FASEB journal Medium 24760752
1997 CD52 expression on sperm is regulated by epididymal maturation: the percentage of sperm expressing CD52 increases progressively from 0.5% in spermatocoeles to 85.7% in the cauda epididymidis, tracking acquisition of motility. CD52 levels on sperm positively correlate with percentage of motile cells, suggesting involvement in sperm maturation. Flow cytometry with CAMPATH-1G, quantitative immunostaining of sperm from different epididymal regions Molecular human reproduction Medium 9464849
1996 CD52 mRNA levels in epididymal cells are regulated post-transcriptionally by temperature: exposure to 37°C (vs. 33°C) rapidly and irreversibly suppresses CD52/CE5 mRNA in a specific manner without affecting other epididymal mRNAs, as shown in dog epididymal cell culture; cycloheximide and DRB experiments suggest mRNA half-life regulation. Epididymal cell culture, Northern blot, temperature shift experiments, cycloheximide and DRB treatment Endocrinology Medium 8828507
2002 Peripheral blood myeloid dendritic cells (lineage−HLA-DR+CD11c+) express CD52 and are depleted by alemtuzumab treatment in patients, while tissue-resident Langerhans cells and dermal-interstitial DCs do not express CD52 under steady-state or inflammatory conditions. Depletion of CD52+ cells from normal PB strongly inhibits allogeneic MLR and primary autologous responses to KLH. CD52 expression is lost during monocyte-derived DC maturation with LPS. Four-color flow cytometry, immunohistochemistry of skin and gut, allogeneic MLR, KLH primary response assay, patient sample analysis before/after alemtuzumab Blood Medium 12176892 12393688

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 416 9193354
2003 Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 329 12865797
2003 Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 279 12543862
2009 Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 265 19740383
2003 A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 232 15070664
1998 Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leukemia research 219 9593475
2013 T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nature immunology 165 23685786
1997 Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 161 9215839
1991 Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. European journal of immunology 154 1711975
2013 Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. Journal of immunology (Baltimore, Md. : 1950) 138 24198283
2000 CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone marrow transplantation 136 10918407
2006 Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clinical cancer research : an official journal of the American Association for Cancer Research 116 17145843
2002 Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood 114 12393688
1998 Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology 112 9824507
2002 Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood 109 12176892
1993 The glycosylphosphatidylinositol-anchored lymphocyte antigen CDw52 is associated with the epididymal maturation of human spermatozoa. Journal of reproductive immunology 98 7685389
1993 Efficient complement-mediated lysis of cells containing the CAMPATH-1 (CDw52) antigen. Molecular immunology 95 8366859
2017 The immunological function of CD52 and its targeting in organ transplantation. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 92 28283679
1999 Male-specific modification of human CD52. The Journal of biological chemistry 91 10514467
2003 Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD52 monoclonal antibody, Campath-1H. Cancer research 84 14559836
1993 A major mRNA of the human epididymal principal cells, HE5, encodes the leucocyte differentiation CDw52 antigen peptide backbone. Molecular reproduction and development 82 8418821
1996 Surface and mRNA expression of the CD52 antigen by human eosinophils but not by neutrophils. Blood 80 8977262
1995 Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma. Blood 80 7632956
1995 Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. International immunology 79 7718516
2006 Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer 72 16688777
2018 CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function. Proceedings of the National Academy of Sciences of the United States of America 70 29997173
2009 Variable CD52 expression in mature T cell and NK cell malignancies: implications for alemtuzumab therapy. British journal of haematology 67 19236377
1994 Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin's lymphomas. Journal of clinical pathology 66 8027367
2018 Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis. Clinical and experimental immunology 64 30144037
1997 Interaction of the human epididymal protein CD52 (HE5) with epididymal spermatozoa from men and cynomolgus monkeys. Molecular reproduction and development 61 9291477
2010 Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. Bone marrow transplantation 59 20348971
2001 CD52 antigen--a review. Medical science monitor : international medical journal of experimental and clinical research 56 11257744
2017 CD52 inhibits Toll-like receptor activation of NF-κB and triggers apoptosis to suppress inflammation. Cell death and differentiation 55 29244050
1996 CD52 is the 'major maturation-associated' sperm membrane antigen. Molecular human reproduction 55 9238651
2001 New insights into the origin, structure and role of CD52: a major component of the mammalian sperm glycocalyx. Cells, tissues, organs 52 11114591
2001 Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. Medical oncology (Northwood, London, England) 52 11778765
2011 CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression. Leukemia 49 21394097
2009 Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab. Blood 49 19638623
1996 Body temperature (37 C) specifically down-regulates the messenger ribonucleic acid for the major sperm surface antigen CD52 in epididymal cell culture. Endocrinology 47 8828507
2007 Expression of CD52 in peripheral T-cell lymphoma. Haematologica 46 17488672
1995 Synthetic peptide mimotope of the CAMPATH-1 (CD52) antigen, a small glycosylphosphatidylinositol-anchored glycoprotein. Immunotechnology : an international journal of immunological engineering 44 9373346
2003 Expression of CD52 on plasma cells in plasma cell proliferative disorders. Blood 43 12714489
2017 Depletion of CD52-positive cells inhibits the development of central nervous system autoimmune disease, but deletes an immune-tolerance promoting CD8 T-cell population. Implications for secondary autoimmunity of alemtuzumab in multiple sclerosis. Immunology 42 27925187
2003 Circulating CD20 and CD52 in patients with non-Hodgkin's lymphoma or Hodgkin's disease. British journal of haematology 41 14632776
2007 Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency. The Journal of allergy and clinical immunology 40 18086494
1983 Integration of viral DNA into the genome of the adenovirus type 2-transformed hamster cell line HE5 without loss or alteration of cellular nucleotides. Nucleic acids research 38 6316259
1997 Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria phenotype in human lymphocytes by a novel mechanism. The Biochemical journal 37 9148769
2015 Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. Cytotherapy 36 26549384
1996 Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment. International immunology 36 8671618
2006 CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders. Clinical lymphoma & myeloma 34 16796779
2000 The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells. International immunology 34 10744652
1997 Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients treated with Campath-1H (anti-CD52). European journal of haematology 34 9020367
1997 Human epididymal secreted protein CD52 on ejaculated spermatozoa: correlations with semen characteristics and the effect of its antibody. Molecular human reproduction 34 9464849
2009 Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia. Haematologica 33 19794084
2003 CD52 expression in hairy cell leukemia. American journal of hematology 33 14635201
2014 CD52 is a molecular target in advanced systemic mastocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 24760752
2001 Changes of the major sperm maturation-associated epididymal protein HE5 (CD52) on human ejaculated spermatozoa during incubation. Molecular human reproduction 30 11420384
1992 The distribution of the CDW52 molecule on blood cells and characterization of its involvement in T cell activation. Transplantation 30 1352921
2007 CD52 over-expression affects rituximab-associated complement-mediated cytotoxicity but not antibody-dependent cellular cytotoxicity: preclinical evidence that targeting CD52 with alemtuzumab may reverse acquired resistance to rituximab in non-Hodgkin lymphoma. Leukemia & lymphoma 29 18067019
2005 Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis. Pediatric blood & cancer 29 15390358
1996 Recognition of CD52 allelic gene products by CAMPATH-1H antibodies. Immunology 29 8690449
2024 Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors. Cell reports. Medicine 28 38242120
2021 CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. Frontiers in immunology 28 33658999
2005 CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab. Leukemia & lymphoma 28 16019510
2014 Identification of campath-1 (CD52) as novel drug target in neoplastic stem cells in 5q-patients with MDS and AML. Clinical cancer research : an official journal of the American Association for Cancer Research 27 24799522
1998 Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart. Journal of molecular biology 27 9811544
2015 Cytogenetic and flow cytometry evaluation of Richter syndrome reveals MYC, CDKN2A, IGH alterations with loss of CD52, CD62L and increase of CD71 antigen expression as the most frequent recurrent abnormalities. American journal of clinical pathology 26 25511139
2010 Expeditious chemoenzymatic synthesis of CD52 glycopeptide antigens. Organic & biomolecular chemistry 26 20848033
2008 Cd52, known as a major maturation-associated sperm membrane antigen secreted from the epididymis, is not required for fertilization in the mouse. Genes to cells : devoted to molecular & cellular mechanisms 25 18782223
2015 Characterisation of a Novel Anti-CD52 Antibody with Improved Efficacy and Reduced Immunogenicity. PloS one 24 26372145
2007 CD52 expression in non-mycotic T- and NK/T-cell lymphomas. Leukemia & lymphoma 24 17325855
2005 CD52 expression in Waldenstrom's macroglobulinemia: implications for alemtuzumab therapy and response assessment. Clinical lymphoma 24 15794865
2013 Immune regulation by CD52-expressing CD4 T cells. Cellular & molecular immunology 23 23934027
2005 Different glycoforms of the human GPI-anchored antigen CD52 associate differently with lipid microdomains in leukocytes and sperm membranes. Biochemical and biophysical research communications 23 16266689
2005 Giant cell tumors of the bone: molecular profiling and expression analysis of Ephrin A1 receptor, Claudin 7, CD52, FGFR3 and AMFR. Pathology, research and practice 23 16325507
2004 Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human epididymis. Journal of andrology 23 14662784
2015 Anti-mouse CD52 monoclonal antibody ameliorates intestinal epithelial barrier function in interleukin-10 knockout mice with spontaneous chronic colitis. Immunology 22 25087772
2009 CD52 expression in peripheral T-cell lymphomas determined by combined immunophenotyping using tumor cell specific T-cell receptor antibodies. Leukemia & lymphoma 21 19479612
2008 A novel Raji-Burkitt's lymphoma model for preclinical and mechanistic evaluation of CD52-targeted immunotherapeutic agents. Clinical cancer research : an official journal of the American Association for Cancer Research 21 18223233
2006 Reconstitution of the T-cell repertoire following treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with B-cell chronic lymphocytic leukaemia. British journal of haematology 21 16995884
1999 Structure and chromosomal location of mouse and human CD52 genes. Biochimica et biophysica acta 21 10524207
2021 Regulation of Monocyte Adhesion and Type I Interferon Signaling by CD52 in Patients With Systemic Sclerosis. Arthritis & rheumatology (Hoboken, N.J.) 20 33760395
2016 Alteration of CD39+Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment. Journal of neuroimmunology 20 28087077
2019 Engineering an anti-CD52 antibody for enhanced deamidation stability. mAbs 19 31199181
2006 CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice. Experimental hematology 18 16728276
2005 Kinetic and binding studies with purified recombinant proteins ferredoxin reductase, ferredoxin and cytochrome P450 comprising the morpholine mono-oxygenase from Mycobacterium sp. strain HE5. The FEBS journal 18 15720389
2001 Immunophenotype changes and loss of CD52 expression in two patients with relapsed T-cell prolymphocytic leukaemia. Leukemia & lymphoma 18 11911422
2000 CD52 mRNA is modulated by androgens and temperature in epididymal cell cultures. Molecular reproduction and development 18 10737964
2000 Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G. Cytotherapy 18 12042050
1997 Regionalized expression of CD52 in rat epididymis is related to mRNA poly(A) tail length. Molecular reproduction and development 18 9364437
2023 Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies. Blood advances 17 35475910
2017 Quantitative flow cytometric evaluation of CD200, CD123, CD43 and CD52 as a tool for the differential diagnosis of mature B-cell neoplasms. Revista brasileira de hematologia e hemoterapia 17 28830605
2007 Different levels of CD52 antigen expression evaluated by quantitative fluorescence cytometry are detected on B-lymphocytes, CD 34+ cells and tumor cells of patients with chronic B-cell lymphoproliferative diseases. Cytometry. Part B, Clinical cytometry 17 17428002
2002 Phenotypic transformation of CD52(pos) to CD52(neg) leukemic T cells as a mechanism for resistance to CAMPATH-1H. Leukemia 17 11986948
2002 Analysis of a human sperm CD52 glycoform in primates: identification of an animal model for immunocontraceptive vaccine development. Biology of reproduction 17 12021047
2001 A cytochrome P450 and a ferredoxin isolated from Mycobacterium sp. strain HE5 after growth on morpholine. Applied microbiology and biotechnology 17 11549020
2018 Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis. Journal of neuroinflammation 16 30098594
2002 A male genital tract-specific carbohydrate epitope on human CD52: implications for immunocontraception. Tissue antigens 16 12492811
2024 T-cell dysfunction in CLL is mediated through expression of Siglec-10 ligands CD24 and CD52 on CLL cells. Blood advances 15 39042920
2019 Specific Sialoforms Required for the Immune Suppressive Activity of Human Soluble CD52. Frontiers in immunology 15 31507595

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