Affinage

CD5

T-cell surface glycoprotein CD5 · UniProt P06127

Length
495 aa
Mass
54.6 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD5 is a transmembrane glycoprotein expressed on T cells and a subset of B cells that functions as an inhibitory co-receptor tuning the threshold of antigen-receptor signaling (PMID:10704468, PMID:20952682). Its surface level is set by the strength of the positively selecting TCR-MHC interaction during thymocyte development and parallels TCR avidity, and its cytoplasmic domain is required for its inhibitory role in selection (PMID:9858516, PMID:11313384). Upon TCR engagement, Lck phosphorylates CD5 at Y429 and Y463, with Y429 serving as a docking site for a signalosome of adaptors (c-Cbl, CIN85, CRKL) that allows CD5 to simultaneously engage positive (PI3K) and negative (UBASH3A, SHIP1) TCR-signaling regulators (PMID:11298344, PMID:32434911). In parallel, CD5 constitutively associates with CK2 through the regulatory beta subunit and is phosphorylated by it at Ser459/461; cross-linking activates CD5-associated CK2, and this CK2 axis sets T cell responsiveness and, via AKT-dependent inhibition of GSK3 and activation of mTOR, drives Th17 and Th2 differentiation (PMID:9668105, PMID:22904299, PMID:24356888). CD5 signaling instructs immune outcomes by blocking mTOR to favor peripheral Treg induction, while the signalosome restrains inopportune Foxp3 transactivation (PMID:25786177, PMID:32434911). In B cells, CD5 raises the BCR signaling threshold to enforce tolerance of anergic and autoreactive cells and promotes B cell survival through autocrine IL-10 (PMID:10704468, PMID:12393419). The extracellular SRCR domains engage CD72 and also mediate homophilic CD5-CD5 interactions through domain 1, both contributing inhibitory tuning, and CD5-CD72 engagement supports Treg and IL-10+ Breg homeostasis (PMID:1711157, PMID:20952682, PMID:24950378). Surface CD5 abundance is further controlled by alternative exon-1 usage (membrane E1A versus intracellularly retained E1B), IL-6-driven promoter demethylation, and post-transcriptional control by alternative polyadenylation, PTBP1, and miR-204 (PMID:15998834, PMID:19380809, PMID:27005442). CD5 on dendritic cells is required to prime optimally protective CD5hi T helper and CD8+ T cells, and its inhibitory function in effector T cells is therapeutically relevant: CD5 deletion enhances CAR T cell antitumor activity (PMID:36795805, PMID:39028827).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1991 High

    Identifying a physiological CD5 ligand addressed how CD5's extracellular domain engages partner cells, establishing CD72 as a B-cell counter-receptor.

    Evidence Biotin-labeled CD5 binding to B cells, anti-CD72 antibody blocking, and CD72 cDNA transfection conferring binding to non-B cells

    PMID:1711157

    Open questions at the time
    • Did not establish the downstream signaling consequence of CD5-CD72 engagement
    • Affinity and stoichiometry of the interaction not defined
  2. 1998 High

    Defining cytoplasmic-domain binding partners revealed how CD5 transduces signals, identifying a constitutive CK2 association and serine phosphorylation as a core effector mechanism.

    Evidence Yeast two-hybrid screen, reciprocal co-IP in B and T cell lines and splenocytes, in vitro kinase assay mapping Ser459/461, and CD5 cross-linking

    PMID:9668105

    Open questions at the time
    • Did not define the functional output of CK2 activation at the time
    • Additional cytoplasmic partners (CaMKIIdelta, Tctex-1) reported separately at Medium confidence
  3. 1998 High

    Linking CD5 surface levels to TCR signal strength explained why CD5 expression varies, establishing it as a readout and rheostat of TCR avidity during selection.

    Evidence Flow cytometry across pre-TCR-deficient, lck-deficient, and TCR transgenic mouse models

    PMID:9858516

    Open questions at the time
    • Did not resolve the molecular signal that sets the expression set-point
    • Causality of CD5 level on selection outcome shown in a later study
  4. 2000 High

    Testing CD5 in a B-cell anergy model established that CD5 enforces B-cell tolerance by negatively regulating BCR signaling.

    Evidence CD5-KO crossed to HEL/sHEL anergy model with anti-HEL IgM ELISA, proliferation, and Ca2+ flux readouts

    PMID:10704468

    Open questions at the time
    • Did not identify the cytoplasmic effectors mediating BCR inhibition
    • Mechanism of recruitment to the BCR not defined
  5. 2001 High

    Mapping CD5 tyrosine phosphorylation sites and the responsible kinase clarified how TCR engagement activates CD5, showing Lck-dependent phosphorylation at Y429 and Y463.

    Evidence Tyrosine-mutant transfectants, in vitro kinase assays with recombinant Lck and Fyn, and Lck-deficient Jurkat cells

    PMID:11298344

    Open questions at the time
    • Did not identify the effectors recruited to phosphorylated tyrosines
    • Relative roles of Y429 vs Y463 not resolved
  6. 2001 High

    Genetic dissection showed the CD5 cytoplasmic domain is required for inhibitory function and that CD5 dosage shifts the balance between positive and negative thymocyte selection.

    Evidence CD5 overexpression, cytoplasmic-truncation knock-in, and KO mice in TCR transgenic crosses scored for selection outcomes

    PMID:11313384

    Open questions at the time
    • Did not assign the relevant cytoplasmic motif
    • Connection to specific downstream pathway left open
  7. 2002 High

    Demonstrating CD5-driven autocrine IL-10 revealed a pro-survival output beyond signal inhibition, linking CD5 to B-cell persistence.

    Evidence CD5 transfection into CD5- B cells with IL-10 promoter reporter, RT-PCR, Ca2+ flux, and apoptosis assays

    PMID:12393419

    Open questions at the time
    • Transcription factors coupling CD5 to the IL-10 promoter not fully defined here
    • In vivo relevance to B-cell survival not directly tested
  8. 2005 Medium

    Discovery of the B-cell-specific E1B exon explained a mechanism for tuning surface CD5, showing an intracellularly retained isoform that lowers membrane CD5.

    Evidence Alternative exon sequencing, RT-PCR across B-cell subsets, E1B transfection into Jurkat cells with flow cytometry

    PMID:15998834

    Open questions at the time
    • Single lab; physiological regulators of E1A/E1B choice not established here
    • Functional consequence shown only as reduced membrane expression
  9. 2009 Medium

    Connecting IL-6 to CD5-E1B promoter methylation defined an inflammatory-cytokine route that lowers membrane CD5 in SLE B cells.

    Evidence Bisulfite sequencing, methylation-sensitive endonuclease assays, isoform RT-PCR, and anti-IL6R blockade in SLE vs healthy B cells

    PMID:19380809

    Open questions at the time
    • Single lab; causal contribution to SLE pathology not established
    • DNMT1 link not validated by genetic perturbation
  10. 2010 High

    Identifying homophilic CD5-CD5 binding through domain 1 revealed an additional inhibitory engagement mode independent of CD72.

    Evidence Soluble CD5 binding assays, domain-1 mutagenesis, blocking mAb IgG/Fab, and T-cell activation and rat lymph node functional assays

    PMID:20952682

    Open questions at the time
    • Physiological context of homophilic engagement in vivo not defined
    • Relationship between homophilic binding and CD72 binding not resolved
  11. 2012 High

    A CK2-binding-domain knock-in mouse established that CD5-CK2 signaling sets T-cell responsiveness and selectively drives Th2/Th17 differentiation, phenocopying CD5-KO.

    Evidence CD5ΔECK2BD knock-in mice with proliferation, AICD, Th differentiation, EAE, and high-dose tolerance assays

    PMID:22904299

    Open questions at the time
    • Did not detail the intracellular pathway downstream of CK2 at this stage
    • Th1 differentiation unaffected, leaving lineage selectivity mechanism open
  12. 2014 High

    Mechanistic dissection placed CD5-CK2 upstream of AKT, defining GSK3 inhibition and mTOR activation as the route by which CD5 stabilizes Th17 differentiation.

    Evidence CD5ΔECK2BD mice with AKT/GSK3/mTOR/S6K phospho-westerns, RORγt confocal imaging, and IFN-γ sensitivity assays

    PMID:24356888

    Open questions at the time
    • Direct CK2 substrate linking to AKT not pinpointed
    • Generalizability to human Th17 left to a separate study
  13. 2015 High

    Linking CD5 to extrathymic Treg induction showed CD5 promotes Treg conversion by blocking mTOR, protecting cells from bystander-cytokine inhibition.

    Evidence CD5-KO and transgenic mice in Treg induction assays with IL-4/IL-6/IFN-γ and mTOR readouts

    PMID:25786177

    Open questions at the time
    • Reconciliation with pro-mTOR Th17 role not fully resolved
    • Molecular link between CD5 and mTOR suppression in this context not detailed
  14. 2016 Medium

    Post-transcriptional analysis revealed that APA, PTBP1, and miR-204 shorten the CD5 3'UTR upon TCR activation to raise CD5 output.

    Evidence 3'UTR reporters, isoform RT-PCR in primary and Jurkat T cells, PTBP1 siRNA, and PTBP1 poly(A) binding assay

    PMID:27005442

    Open questions at the time
    • Single lab; impact on endogenous CD5 protein levels not quantified
    • Interplay with transcriptional/isoform regulation not integrated
  15. 2017 High

    Defining a cytoplasmic CK2-CD5-BLNK-STAT3 complex in CLL showed CD5 sustains constitutive STAT3 Ser727 phosphorylation in malignant B cells.

    Evidence Mass-spec co-IP, reciprocal co-IP, in vitro CK2 kinase assay on recombinant STAT3, CD5/BLNK siRNA, neutralizing antibodies, and fractionation

    PMID:28130399

    Open questions at the time
    • Whether the complex operates similarly in normal B cells not established
    • Functional consequence for CLL survival not directly tested here
  16. 2020 High

    Phosphoproteomics defined the Y429 signalosome, showing c-Cbl coordinates simultaneous recruitment of positive (PI3K) and negative (UBASH3A, SHIP1) regulators and restrains peripheral Treg induction.

    Evidence Quantitative mass spectrometry, Y429-mutant knock-in mice, co-IP, and in vivo Treg/Foxp3 reporter assays

    PMID:32434911

    Open questions at the time
    • Stoichiometry and dynamics of competing positive/negative branches not resolved
    • How signalosome integrates with the CK2 axis not defined
  17. 2023 High

    Studying CD5 on dendritic cells revealed a cell-extrinsic role: DC CD5 is required to prime optimally protective CD5hi T helper and CD8+ T cells and shapes responses to checkpoint blockade.

    Evidence In vivo tumor models, conditional CD5 deletion in T cells, human melanoma lymph-node DC analysis, ICB studies, and IL-6 manipulation of DC differentiation

    PMID:36795805

    Open questions at the time
    • Molecular mechanism by which DC CD5 instructs T-cell priming not detailed
    • Ligand engaged by DC CD5 during priming not identified
  18. 2024 High

    CRISPR knockout established CD5 as a brake on effector T cells with therapeutic implications, as CD5 deletion enhances CAR T-cell antitumor function.

    Evidence CRISPR-Cas9 CD5 KO in CAR T cells with in vitro cytotoxicity and in vivo hematological and solid tumor models

    PMID:39028827

    Open questions at the time
    • The cytoplasmic effector responsible for the inhibitory brake in CAR T cells not isolated
    • Long-term safety and exhaustion phenotype not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the CK2-serine axis and the Y429 tyrosine signalosome are functionally integrated, and which engagements (CD72, homophilic, microbial β-glucan) dominate in each cellular context, remains unresolved.
  • No unified model coupling CK2-driven and tyrosine-driven branches
  • Context-specific dominance among CD5 ligands not established
  • Structural basis of CD5 signaling outputs lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
BLNKCBLCD72CRKLCSNK2BLCKSH3KBP1STAT3
Complex memberships
CD5 Y429 signalosome (c-Cbl/CIN85/CRKL/UBASH3A/SHIP1)CD5-CK2 complexCK2-CD5-BLNK-STAT3 complex (CLL)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CD72 (Lyb-2 in mice) is the ligand for CD5. CD5 protein, labelled with biotin, specifically bound to B-cell surface CD72; this binding was blocked by anti-CD72 antibodies but not other anti-B-cell antibodies. Non-B cells transfected with human CD72 cDNA gained ability to bind CD5-biotin conjugate. Biotin-labeled CD5 used as probe on cells; blocking with anti-CD72 antibodies; transfection of CD72 cDNA into non-B cells (mouse L-cells and Jurkat T cells) Nature High 1711157
1998 The beta subunit of casein kinase 2 (CK2) interacts specifically with the cytoplasmic domain of CD5. CK2 holoenzyme associates constitutively with CD5 in human and murine B and T cell lines and murine splenocytes, mediated by the amino terminus of the CK2 regulatory beta subunit. CK2 binds and phosphorylates CD5 at Ser459 and Ser461 (CK2 motifs). Cross-linking of CD5 activates CD5-associated CK2 independently of net CK2 recruitment, and this activation is not triggered by BCR or TCR cross-linking. Yeast two-hybrid screen; co-immunoprecipitation in human and murine B and T cell lines and splenocytes; in vitro kinase assay; CD5 cross-linking The Journal of biological chemistry High 9668105
1998 The cytoplasmic domain of CD5 interacts with Ca2+/calmodulin-dependent kinase IIdelta (CaMKIIdelta) and with Tctex-1 (a dynein light chain component). The CaMKIIdelta interaction was confirmed in vitro using fusion proteins. Yeast two-hybrid screen; in vitro binding assay with fusion proteins European journal of immunology Medium 9692886
1998 CD5 surface expression during thymocyte development is regulated by TCR signals: low-level expression on DN thymocytes requires pre-TCR engagement and p56(lck) activity; DP thymocyte CD5 levels are maintained by low-affinity TCR-MHC interactions; high-level CD5 is induced by positively or negatively selecting TCR-MHC ligands. CD5 surface expression on mature T cells directly parallels TCR avidity/signaling intensity of the positively selecting interaction. Analysis of CD5 expression in mice with defined developmental and signal transduction defects (pre-TCR deficient, lck-deficient, TCR transgenic); flow cytometry The Journal of experimental medicine High 9858516
2001 The cytoplasmic domain of CD5 is required for its inhibitory function in thymocyte selection. A transgene encoding a truncated (cytoplasmic domain-deleted) form of CD5 failed to rescue the CD5-/- phenotype in thymocyte selection. CD5 overexpression or deletion shifted thymocyte selection toward positive or negative selection, respectively, in a manner dependent on TCR avidity and basal CD5 expression levels. CD5 transgenic mice (overexpression and truncation knock-in); CD5-/- mice; TCR transgenic crosses; analysis of thymocyte selection outcomes Journal of immunology (Baltimore, Md. : 1950) High 11313384
2000 CD5 negatively regulates BCR signaling in anergic B cells to maintain B cell tolerance. CD5-/- mice in the HEL/sHEL anergy model showed loss of B cell tolerance (elevated anti-HEL IgM), and 'anergic' B cells lacking CD5 had enhanced proliferative responses and elevated intracellular Ca2+ at rest and after IgM cross-linking. CD5 knockout mice crossed with HEL transgenic anergy model; serum ELISA for anti-HEL IgM; in vitro proliferation assay; intracellular Ca2+ measurement The Journal of experimental medicine High 10704468
2002 CD5 promotes B cell survival by stimulating autocrine IL-10 production. Introduction of CD5 into CD5- B cells activated the IL-10 promoter and induced IL-10 mRNA and protein. The cytoplasmic domain of CD5 was sufficient for this effect. CD5 also protected normal human B cells from apoptosis after BCR stimulation while reducing BCR-induced Ca2+ responses. Transfection of CD5 into CD5- B cells; IL-10 promoter reporter assay; RT-PCR for IL-10 mRNA; Ca2+ flux measurement; apoptosis assay Blood High 12393419
2001 CD5 functions as a negative regulator of BCR signaling and may help prevent inappropriate activation of autoreactive B-1a cells. Review summarizing CD5-/- mouse data and B-1a cell biology (mechanistic context from experimental literature) Annual review of immunology Low 11861604
2001 Residues Y429 and Y463 of human CD5 are phosphorylated in vivo by protein tyrosine kinases following T cell stimulation. In vitro kinase assays with purified recombinant Lck and Fyn confirmed direct phosphorylation at these sites. Lck-deficient Jurkat cells showed absent CD5 tyrosine phosphorylation, establishing that Lck is required for CD5 tyrosine phosphorylation. Tyrosine-mutated CD5 transfectants in Jurkat cells; anti-CD3 mAb and pervanadate stimulation; in vitro kinase assays with recombinant Lck and Fyn; analysis in Lck-deficient and CD3-deficient Jurkat cells European journal of immunology High 11298344
2005 An alternative exon 1 (E1B) of the human CD5 gene, found exclusively in B lymphocytes, encodes a truncated protein that is retained intracellularly rather than transported to the membrane. Presence of E1B-containing transcripts reduces E1A-containing transcript levels and diminishes membrane CD5 expression. Introduction of E1B into Jurkat cells reduced membrane CD5 expression. E1B contains sequence of a defective human endogenous retrovirus. Identification of alternative exon by sequencing; RT-PCR in B cell subsets including CLL and pre-B cells; transfection of E1B into Jurkat cells with flow cytometric assessment of membrane CD5; bisulfite/methylation analysis Blood Medium 15998834
2009 In SLE B cells, IL-6 prevents DNMT1 induction, leading to demethylation of the CD5-E1B promoter. This causes preferential transcription of CD5-E1B at the expense of CD5-E1A, reducing membrane CD5 expression. BCR engagement amplifies this effect. Blocking IL-6 receptor reverses the demethylation. Bisulfite sequencing; methylation-sensitive endonuclease assays; RT-PCR for E1A and E1B isoforms; IL-6 receptor blocking antibody; DNMT1 expression analysis in SLE vs healthy B cells Journal of immunology (Baltimore, Md. : 1950) Medium 19380809
2010 CD5 mediates species-specific homophilic interactions (CD5 is a ligand for itself). Only CD5 domain 1 is involved. CD5 monoclonal antibodies that have functional effects block homophilic binding. Inhibition of CD5 domain 1 engagement (by mutation or by IgG/Fab from a blocking mAb) increased antigen-specific T cell responses in vitro, and a blocking Fab enhanced polyclonal immune responses of rat lymph node cells, demonstrating that homophilic CD5 binding exerts inhibitory function. Soluble CD5 purified at neutral pH; binding assays; site-directed mutation of domain 1; blocking monoclonal antibodies (IgG and Fab fragments); in vitro T cell activation assays; rat lymph node polyclonal stimulation assay Journal of immunology (Baltimore, Md. : 1950) High 20952682
2012 CD5-dependent CK2 activation sets the threshold for T cell responsiveness. A CD5 knock-in mouse with selective deletion of the CK2-binding domain (CD5ΔECK2BD) showed hypoproliferation, enhanced activation-induced cell death, and defective Th2 and Th17 (but not Th1) differentiation of CD4+ T cells upon stimulation. CD5ΔECK2BD mice recapitulated the reduced EAE severity of CD5-KO mice and were unable to generate high-dose tolerance, phenocopying CD5-KO. Knock-in mouse with microdeletion of CK2-binding domain in CD5; T cell proliferation assays; activation-induced cell death measurement; Th differentiation assays in vitro and in vivo; EAE model; high-dose tolerance assay Journal of immunology (Baltimore, Md. : 1950) High 22904299
2014 CD5-CK2 signaling promotes Th17 differentiation via two independent mechanisms: inhibition of GSK3 and activation of mTOR, both downstream of AKT. Loss of CD5-CK2 signaling reduced AKT activation, increased GSK3 activity, sensitized Th17 cells to IFN-γ-mediated inhibition, decreased S6K activity, and attenuated nuclear translocation of RORγt. CD5ΔECK2BD knock-in mice; in vitro Th17 differentiation assays; AKT/GSK3/mTOR/S6K phosphorylation by western blot; RORγt nuclear localization by confocal microscopy; IFN-γ sensitivity assays European journal of immunology High 24356888
2015 CD5 instructs extrathymic regulatory T cell (Treg) induction by blocking mTOR activation. CD5hi T cells were resistant to inhibition of Treg induction by IL-4, IL-6, and IFN-γ from bystander lymphocytes, while Cd5-/- and CD5lo T cells were sensitized. CD5 promoted Treg cell conversion by blocking mTOR activation. CD5-/- mice; CD5 transgenic mice; in vitro Treg induction assays with bystander cytokines; mTOR activity measurement; flow cytometric analysis of FoxP3+ Treg conversion Immunity High 25786177
2011 CD5 costimulation promotes stable human Th17 development by prolonging STAT3 activation and upregulating IL-23 receptor (IL-23R) expression. Compared with CD28 costimulation, CD5 costimulation induced more IL-17-producing cells, increased RORγt levels, and critically depended on CD5-induced IL-23R elevation. Human naive T cell differentiation assays with CD5, CD6, or CD28 costimulation; intracellular cytokine staining; STAT3 phosphorylation kinetics; IL-23R expression by flow cytometry; RORγt measurement Blood Medium 21926348
2017 In CLL cells, CD5 is part of a CK2–CD5–BLNK–STAT3 complex that is required for constitutive serine 727 phosphorylation of STAT3. In vitro, activated CK2 directly phosphorylated recombinant STAT3 on Ser727. siRNA knockdown of CD5 or BLNK, and CD5-neutralizing antibodies, significantly reduced pSTAT3 levels. Fractionation showed the complex resides in the cytoplasm, while pSTAT3 is shuttled to the nucleus. Mass spectrometry co-immunoprecipitation; reciprocal co-IP for CK2, CD5, BLNK, STAT3; in vitro kinase assay with recombinant STAT3; siRNA knockdown; CD5-neutralizing antibodies; confocal microscopy; subcellular fractionation Molecular cancer research : MCR High 28130399
2016 CD5 mRNA expression in human T cells is regulated post-transcriptionally by alternative polyadenylation (APA), PTBP1, and miR-204. Upon TCR activation, shorter 3'-UTR CD5 mRNA isoforms are preferentially expressed. PTBP1 directly binds the proximal poly(A) signal and PTBP1 siRNA depletion reduces mRNA from that poly(A) site. Shorter isoforms confer higher reporter expression in activated T cells, and the longer isoform is subject to miR-204-mediated repression. 3'-UTR reporter assays; RT-PCR for CD5 isoforms in primary human T cells and Jurkat cells; siRNA knockdown of PTBP1; RNA binding assay for PTBP1 to poly(A) signal European journal of immunology Medium 27005442
2020 CD5 signalosome in primary T cells: TCR engagement induces phosphorylation of CD5 tyrosine 429, which serves as a docking site for adaptor proteins c-Cbl, CIN85, and CRKL. c-Cbl acts as a coordinator enabling CD5 to simultaneously engage positive (PI3K) and negative (UBASH3A, SHIP1) regulators of TCR signaling. Disruption of the CD5 signalosome (mutant mice) selectively represses Foxp3 transactivation and limits inopportune peripheral Treg induction during responses to foreign antigen. Quantitative mass spectrometry; genetic studies in mutant mice (Y429 mutation); phosphoproteomics; co-immunoprecipitation; in vitro and in vivo Treg induction assays; Foxp3 reporter Proceedings of the National Academy of Sciences of the United States of America High 32434911
1998 CD5 binds a novel B-cell surface ligand (CD5L, distinct from CD72) composed of 77–80 and 38–40 kDa polypeptide chains. CD5-Ig fusion protein induced proliferation of resting B cells and bound this ligand on activated splenic B cells and peritoneal B cells but not T cells. Anti-CD72 antibodies did not block CD5-Ig binding, and CD5-Ig did not bind CD72-transfected cells, ruling out CD72 as the binding partner in this context. CD5-Ig chimeric fusion protein binding assays; flow cytometry with anti-CD72 blocking antibodies; immunoprecipitation of surface-labeled B cell molecules with CD5-Ig; transfection of CD72 into non-B cells (negative result for CD5-Ig binding) International immunology Medium 9723705
1999 Recombinant soluble CD5 extracellular domain binds a broadly distributed alternative cell surface receptor on monocytes, lymphocytes, and various cell lines (lymphoid, myelomonocytic, epithelial). This binding is divalent cation-independent and inhibited by high concentrations of certain monosaccharides. Natural soluble CD5 from human serum and CD5-Ig fusion proteins compete with recombinant soluble CD5 for this binding. CD5 SRCR domains D1 and D2 are involved. Recombinant soluble CD5 extracellular domain glycoprotein cell binding assays; competition with monosaccharides, CD5-Ig fusion proteins, and natural soluble CD5; domain-deletion competition assays European journal of immunology Medium 10427974
2011 The full-length CD5 protein variant (encoded by E1A) translocates SHP-1 (SH2-containing phosphatase 1) to the vicinity of the BCR, raises the BCR signaling threshold, and limits responses of autoreactive B cells. The truncated variant (encoded by E1B) remains in the cytoplasm along with SHP-1, preventing this negative regulatory function. Review synthesizing transfection and biochemical studies from prior publications (mechanistic summary based on experimental data from the laboratory) Critical reviews in immunology Low 21395509
2011 CD5 expression promotes constitutive activation of ERK1/2, PI3K/mTOR, and calcineurin-NFAT signaling pathways in B lymphocytes, and changes in IL-10 production are related to activation of transcription factors NFAT2 and STAT3. CD5 transfection into B cells; western blot for phosphorylated signaling intermediates; transcription factor activation assays; IL-10 measurement Autoimmunity reviews Low 22349614
2011 CD5 expression on dendritic cells is required to generate optimally protective CD5hi T helper and CD8+ T cells. Activating CD5 on DCs enhanced T cell priming. CD5+ DC numbers increased during immune checkpoint blockade (ICB) therapy. Deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Low IL-6 concentrations promoted de novo differentiation of CD5+ DCs. In vivo mouse tumor models; conditional CD5 deletion from T cells; DC subset analysis in human melanoma-affected lymph nodes; ICB therapy studies; IL-6 concentration manipulation for DC differentiation Science (New York, N.Y.) High 36795805
2024 CD5 inhibits CAR T cell activation. CRISPR-Cas9 knockout of CD5 enhances CAR T cell antitumor effect in multiple hematological and solid cancer models by driving increased effector function, enhanced cytotoxicity, in vivo expansion, and persistence without apparent toxicity. CRISPR-Cas9 CD5 KO in CAR T cells; in vitro cytotoxicity assays; in vivo mouse tumor models with hematological and solid cancers; flow cytometric analysis of expansion and persistence Science immunology High 39028827
2014 CD5-CD72 interaction maintains regulatory T and B cell homeostasis. Blockade of CD5 or CD72 with neutralizing antibodies reduced both IL-10-expressing Bregs and FoxP3+ Tregs in co-culture. FoxP3+CD4+ Tregs were reduced in CD19-Cre mice deficient in B-cell-surface CD5. Cell culture with neutralizing antibodies against CD5 and CD72; flow cytometric analysis of Treg and Breg populations; CD19-Cre conditional B-cell CD5 deficient mice Immunological investigations Medium 24950378
2011 The nonsynonymous A471V substitution (rs2229177) in the CD5 cytoplasmic domain affects MAPK cascade activation. Cross-linking of CD5 revealed significant differences between A471V variants in MAPK pathway activation in COS7 cells and human PBMCs. The A471V variants also differ in MAPK activation and IL-8 release upon exposure to Zymosan (a β-glucan-rich fungal particle) in HEK293 cell transfectants, indicating CD5 recognizes microbial β-glucans and that A471V modulates this response. Anti-CD5 mAb cross-linking; western blot for MAPK activation; HEK293 cell transfectants expressing A471V variants; Zymosan stimulation; IL-8 ELISA Molecular biology and evolution Medium 21998275

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Origins and functions of B-1 cells with notes on the role of CD5. Annual review of immunology 543 11861604
1998 CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. The Journal of experimental medicine 522 9858516
1989 CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire. Immunology today 462 2482031
1991 The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature 307 1711157
2001 Fine tuning of TCR signaling by CD5. Journal of immunology (Baltimore, Md. : 1950) 226 11313384
2003 Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood 190 14630808
2002 Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production. Blood 170 12393419
2000 CD5 maintains tolerance in anergic B cells. The Journal of experimental medicine 149 10704468
1999 CD5 expression in human B-cell populations. Immunology today 136 10379049
2009 IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. Journal of immunology (Baltimore, Md. : 1950) 132 19380809
2002 CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes. Blood 132 12406905
1994 Distinctive developmental origins and specificities of murine CD5+ B cells. Immunological reviews 124 7518415
1994 CD5 expression in thymic carcinoma. The American journal of pathology 115 7519823
2012 CD19+CD5+ cells as indicators of preeclampsia. Hypertension (Dallas, Tex. : 1979) 109 22353610
2023 CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses. Science (New York, N.Y.) 106 36795805
2008 CD5: a safeguard against autoimmunity and a shield for cancer cells. Autoimmunity reviews 104 19041428
2015 CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens. Immunity 94 25786177
1990 Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus. The Journal of clinical investigation 90 1688569
1989 Cell surface antigen CD5 is a marker for activated human B cells. European journal of immunology 90 2474446
2002 CD5- mantle cell lymphoma. American journal of clinical pathology 89 12162681
1994 Lymphocyte populations and immune responses in CD5-deficient mice. European journal of immunology 89 7517879
1989 Organization and expression of VH gene families preferentially expressed by Ly-1+ (CD5) B cells. European journal of immunology 82 2480903
2018 CD5, an Undercover Regulator of TCR Signaling. Frontiers in immunology 80 30581443
2011 The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease. Current opinion in immunology 76 21482089
1998 Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5. The Journal of biological chemistry 76 9668105
1990 The peritoneal Ly-1 (CD5) B cell repertoire is unique among murine B cell repertoires. European journal of immunology 74 1690657
2019 The multiple faces of CD5. Journal of leukocyte biology 71 30676652
2003 B-cell lymphomas with coexpression of CD5 and CD10. American journal of clinical pathology 70 12579992
1989 Expression and regulation of CD5 on in vitro activated human B cells. European journal of immunology 69 2472277
1991 CD5+ B cells in autoimmune disease and lymphoid malignancy. Clinical immunology and immunopathology 67 1706969
1993 Autoimmunity-prone B-1 (CD5 B) cells, natural antibodies and self recognition. Autoimmunity 63 7511005
2009 Adult BM generates CD5+ B1 cells containing abundant N-region additions. European journal of immunology 62 19714574
1996 Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics. Clinical and experimental immunology 61 8565316
2004 Genome-wide array-based comparative genomic hybridization of diffuse large B-cell lymphoma: comparison between CD5-positive and CD5-negative cases. Cancer research 59 15342373
2005 An alternative exon 1 of the CD5 gene regulates CD5 expression in human B lymphocytes. Blood 58 15998834
2013 Recent advances in de novo CD5+ diffuse large B cell lymphoma. American journal of hematology 56 23695956
2008 CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells. Journal of leukocyte biology 56 18708592
2004 The CD5+ B-cell. The international journal of biochemistry & cell biology 56 15313456
2000 CD5 signal transduction: positive or negative modulation of antigen receptor signaling. Critical reviews in immunology 54 11100806
1998 A role for CD5 in cognate interactions between T cells and B cells, and identification of a novel ligand for CD5. International immunology 53 9723705
1999 Interaction of recombinant and natural soluble CD5 forms with an alternative cell surface ligand. European journal of immunology 52 10427974
2024 Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas. Blood 51 38145560
2012 CD5-dependent CK2 activation pathway regulates threshold for T cell anergy. Journal of immunology (Baltimore, Md. : 1950) 50 22904299
2006 Expression profiling analysis of the CD5+ diffuse large B-cell lymphoma subgroup: development of a CD5 signature. Cancer science 50 16856881
2002 CD5, an important regulator of lymphocyte selection and immune tolerance. Immunologic research 50 12403363
1999 Quantitative analysis of CD79b, CD5 and CD19 in mature B-cell lymphoproliferative disorders. Haematologica 49 10329919
1991 Auto- and polyreactivity of IgM from CD5+ and CD5- cord blood B cells. Scandinavian journal of immunology 49 1707183
2015 Perspectives on fetal derived CD5+ B1 B cells. European journal of immunology 48 26339791
2013 T-cell modulatory properties of CD5 and its role in antitumor immune responses. Oncoimmunology 48 23483035
2010 A ligand for CD5 is CD5. Journal of immunology (Baltimore, Md. : 1950) 48 20952682
2005 CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clinical lymphoma 45 15794857
1992 Variable gene usage, physiology and development of Ly-1+ (CD5+) B cells. Current opinion in immunology 45 1376603
1999 The role of CD5-expressing B cells in health and disease (review). International journal of molecular medicine 44 10028047
2011 CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation. Blood 43 21926348
2024 CD5 deletion enhances the antitumor activity of adoptive T cell therapies. Science immunology 42 39028827
1992 Analysis of the expression of CD5 by human B cells and correlation with functional activity. Cellular immunology 41 1370255
2007 The paradox of CD5-expressing B cells in systemic lupus erythematosus. Autoimmunity reviews 40 18035326
2016 CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204. European journal of immunology 37 27005442
1998 Interaction of the CD5 cytoplasmic domain with the Ca2+/calmodulin-dependent kinase IIdelta. European journal of immunology 37 9692886
2014 Interaction of CD5 and CD72 is involved in regulatory T and B cell homeostasis. Immunological investigations 36 24950378
2000 Genomic organization of the human CD5 gene. Immunogenetics 35 11061284
2002 CD5+ follicular lymphoma: a clinicopathologic study of three cases. American journal of clinical pathology 34 12375647
1989 The expression and function of CD3 and CD5 in patients with primary Sjögren's syndrome. Arthritis and rheumatism 34 2468337
2012 CD5 expression promotes multiple intracellular signaling pathways in B lymphocyte. Autoimmunity reviews 33 22349614
1990 Contribution of the CD5+ B cell to D-proximal VH family expression early in ontogeny. Journal of immunology (Baltimore, Md. : 1950) 33 1698861
2010 CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation. Leukemia 32 20357824
1993 Peripheral human CD5+ and CD5- B cells may express somatically mutated VH5- and VH6-encoded IgM receptors. Journal of immunology (Baltimore, Md. : 1950) 32 7505018
1991 CD5+ B cells and CD4-8-T cells in neuroimmunological diseases. Journal of neuroimmunology 31 1826505
2020 Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies. Stem cell reviews and reports 30 32008159
2015 CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 30 25743023
1997 Blood group antibodies are made by CD5+ and by CD5- B cells. Immunology and cell biology 30 9429896
2011 CD5 expression in B cells from patients with systemic lupus erythematosus. Critical reviews in immunology 29 21395509
2007 Cytogenetic aberrations and immunoglobulin VH gene mutations in clinically benign CD5- monoclonal B-cell lymphocytosis. American journal of clinical pathology 28 17638670
1994 Expression of CD5 and CD38 by human CD5- B cells: requirement for special stimuli. European journal of immunology 28 7515814
2020 De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances. Clinical lymphoma, myeloma & leukemia 27 32694049
2017 Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR-B1. European journal of immunology 27 28504304
1999 CD5- small B-cell leukemias are rarely classifiable as chronic lymphocytic leukemia. American journal of clinical pathology 27 9894463
2020 Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents. Cells 26 33287301
2018 T Cell Calcium Signaling Regulation by the Co-Receptor CD5. International journal of molecular sciences 25 29701673
1992 CD20 and CD5 expression in B-chronic lymphocytic leukemia. Annals of the New York Academy of Sciences 25 1376065
2017 TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which decreases in contact hypersensitivity. Molecular immunology 24 28505514
2001 Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS. Internal medicine (Tokyo, Japan) 24 11579948
2017 Constitutive Phosphorylation of STAT3 by the CK2-BLNK-CD5 Complex. Molecular cancer research : MCR 23 28130399
2020 CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens. Proceedings of the National Academy of Sciences of the United States of America 22 32434911
2015 CD5 as a Target for Immune-Based Therapies. Critical reviews in immunology 22 26351145
2014 CD5 enhances Th17-cell differentiation by regulating IFN-γ response and RORγt localization. European journal of immunology 22 24356888
2013 Clinicopathologic features of CD5-positive nodal marginal zone lymphoma. American journal of clinical pathology 22 24124149
2005 Analysis of RAG expression by peripheral blood CD5+ and CD5- B cells of patients with childhood systemic lupus erythematosus. Annals of the rheumatic diseases 22 16126793
1998 Characterization of porcine CD5 and CD5+ B cells. Clinical and experimental immunology 21 9472686
2021 CD5+ diffuse large B-cell lymphoma: a narrative review. Leukemia & lymphoma 20 34284686
1999 CD5- B-cell lymphoproliferative disorders presenting in blood and bone marrow. A clinicopathologic study of 40 patients. American journal of clinical pathology 20 10191767
2020 CD5 and CD6 as immunoregulatory biomarkers in non-small cell lung cancer. Translational lung cancer research 19 32953486
2001 Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases. European journal of immunology 19 11298344
1999 De novo CD5+ Burkitt lymphoma/leukemia. American journal of clinical pathology 19 10587706
1996 Distinctive developmental origins and specificities of the CD5+ B-cell subset. Seminars in immunology 19 8850297
1993 CD5+ B cells and the immune system. Immunology letters 19 7507466
1990 Characterization of normal human CD3+ CD5- and gamma delta T cell receptor positive T lymphocytes. Clinical and experimental immunology 19 1691061
2024 mRNA-Engineered CD5-CAR-γδTCD5- Cells for the Immunotherapy of T-Cell Acute Lymphoblastic Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39013083
2011 Evolutionary and functional evidence for positive selection at the human CD5 immune receptor gene. Molecular biology and evolution 18 21998275
1993 Expression and function of CD5 and CD28 in patients with rheumatoid arthritis. Immunology 18 7503950

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