Affinage

CD2

T-cell surface antigen CD2 · UniProt P06729

Length
351 aa
Mass
39.4 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD2 is a T and NK cell surface glycoprotein of the immunoglobulin superfamily that functions as a constitutive adhesion receptor and co-stimulatory signal amplifier, lowering the antigen dose threshold for T cell activation. Its N-terminal Ig domain binds CD58 (human) or CD48 (rodent) with low micromolar affinity stabilized by N-glycosylation at Asn65 and salt bridges at the binding interface; lateral receptor mobility on the membrane amplifies this weak interaction into effective cell-cell adhesion (PMID:3313052, PMID:1717480, PMID:1385399, PMID:17172599). The proline-rich cytoplasmic tail recruits a signaling complex including CD3ζ, p59fyn, p56lck, and adaptor CD2BP2, coupling CD2 to PLC-γ1 phosphorylation, Ca²⁺ mobilization, and MAPK activation—with p59fyn serving as the critical upstream kinase and p62dok acting as a negative regulator—while CD2 also engages in cis interactions with CD48 on the same T cell to support TCR signaling (PMID:1351920, PMID:7912674, PMID:11093170, PMID:9843987, PMID:11254695, PMID:35930657). At the immunological synapse, CD2 localizes to an outer corolla where it captures co-stimulatory receptors and amplifies SFK/LAT/PLC-γ1 signaling by ~77% compared to centrally positioned CD2–CD58 contacts, a function counteracted by PD-1 invasion of this domain (PMID:32929275, PMID:19398758).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1987 High

    Identifying CD58 (LFA-3) as the counter-receptor for CD2 established the molecular basis of the T cell adhesion pathway and showed that this interaction provides a co-stimulatory signal for T cell activation.

    Evidence cDNA cloning and expression of LFA-3, functional adhesion assays, and T cell activation with anti-CD2 mAbs plus natural ligand

    PMID:3102975 PMID:3313052

    Open questions at the time
    • Stoichiometry of CD2-CD58 interaction on cell surfaces unknown
    • Structural basis of binding not yet resolved
    • Relative contribution versus TCR/CD3 not quantified
  2. 1989 High

    Mapping the LFA-3 binding site to the N-terminal Ig domain of CD2 (Kd ~0.4 µM) and showing independence from the cytoplasmic tail defined CD2 as a modular receptor with separable adhesion and signaling functions.

    Evidence Baculovirus-expressed truncated CD2 fragments, circular dichroism, binding assays

    PMID:2466941 PMID:2576417

    Open questions at the time
    • Atomic structure of CD2 domain 1 not yet determined
    • Whether post-translational modifications regulate binding affinity unresolved
  3. 1988 High

    Demonstrating that CD2 signaling requires CD3ζ expression established that CD2 does not signal autonomously but is coupled to the TCR/CD3 complex.

    Evidence CD3-deficient Jurkat mutants reconstituted by CD3ζ transfection; Ca²⁺, phosphoinositide, and IL-2 readouts

    PMID:2901344

    Open questions at the time
    • Physical nature of CD2–CD3ζ coupling not identified
    • Whether coupling is direct or via intermediates unknown
  4. 1990 High

    Physical association of CD2 with CD45 phosphatase suggested a mechanism for how CD2 engagement modulates tyrosine phosphorylation cascades at the T cell surface.

    Evidence Chemical crosslinking and co-immunoprecipitation in human and mouse T lymphocytes

    PMID:1970422 PMID:1980615

    Open questions at the time
    • Functional consequence of CD45 dissociation from CD2 not tested genetically
    • Whether CD45 dephosphorylates CD2-associated kinases directly unclear
  5. 1991 High

    Showing that CD2 adhesion is constitutively active while LFA-1 requires TCR activation positioned CD2 as the initiator of T cell–APC contact, and demonstrating that lateral membrane mobility of both CD2 and GPI-anchored LFA-3 amplifies adhesion explained how a low-affinity interaction achieves functional binding.

    Evidence Cell adhesion assays across activation states; reconstituted planar lipid bilayers with FRAP and laminar flow

    PMID:1672642 PMID:1717480

    Open questions at the time
    • In vivo relevance of GPI vs. transmembrane LFA-3 isoforms not established
    • Role of cytoskeletal anchoring of CD2 in mobility regulation not defined
  6. 1992 High

    Multiple concurrent discoveries refined CD2 structure-function: CD3ζ cytoplasmic domain was shown to be necessary and sufficient for CD2 signal coupling; TCR crosslinking was found to upregulate CD2 avidity via its cytoplasmic C-terminus; and N-glycosylation at Asn65 was established as essential for domain 1 stability and ligand binding.

    Evidence CD8α/CD3ζ chimera reconstitution in CD3-deficient Jurkat; CD2 cytoplasmic tail mutagenesis with CD58 binding assays; Asn65Gln mutagenesis with mass spectrometry

    PMID:1351920 PMID:1353888 PMID:1385399

    Open questions at the time
    • Structural mechanism of avidity regulation unknown
    • Whether glycosylation directly contacts LFA-3 or acts indirectly via folding not resolved
  7. 1993 High

    Identification of CD48 as the rodent CD2 ligand with low-affinity direct binding via domain 1 extended the CD2 adhesion paradigm to rodent models used in subsequent knockout studies.

    Evidence Soluble CD48-CD4 chimera binding, sucrose gradient ultracentrifugation, bacterially expressed CD2 domain 1

    PMID:8099016

    Open questions at the time
    • Whether CD48 and CD58 use identical binding surfaces on CD2 not confirmed
    • Glycosylation independence for CD48 binding contrasts with CD58 requirement—mechanistic basis unclear
  8. 1994 High

    Identification of a physical CD2–CD3ζ–p59fyn–p56lck signaling complex provided the first molecular framework for how CD2 engagement activates Src-family kinases.

    Evidence Co-immunoprecipitation, in vitro kinase assays, double immunofluorescence capping in T cells

    PMID:7912674

    Open questions at the time
    • Direct vs. indirect association among complex members not resolved
    • Relative kinase contributions not yet determined
  9. 1998 High

    Discovery of CD2BP2 binding to proline-rich PPPGHR motifs via a GYF domain revealed a cytoplasmic adaptor mechanism for CD2-specific signal enhancement, while demonstration of lck-independent JNK/AP-1 activation defined an alternative CD2 signaling branch.

    Evidence Yeast two-hybrid, NMR of GYF domain, IL-2 reporter in Jurkat; JNK assays in lck-deficient Jurkat lines

    PMID:9727049 PMID:9843987

    Open questions at the time
    • Physiological role of CD2BP2 in primary T cells not tested
    • Upstream activator of JNK in CD2 pathway unidentified
  10. 1999 High

    CD2 knockout mice revealed that CD2 sets a quantitative antigen sensitivity threshold: CD2-deficient T cells require 3–10-fold more antigen for equivalent activation, establishing CD2's non-redundant costimulatory role in vivo.

    Evidence CD2 KO × TCR-transgenic mice, dose-response proliferation, conjugate formation, Ca²⁺ flux

    PMID:10562314

    Open questions at the time
    • In vivo infection or autoimmune phenotypes of CD2 KO not characterized
    • Compensation by LFA-1 pathway quantified only additively in vitro
  11. 2000 High

    Genetic studies using fyn−/− mice and CD2/CD28 double knockouts established p59fyn as the critical upstream kinase for CD2 (regulating PLC-γ1, Vav, PKC-θ, Dok, FAK, Pyk2) and showed CD2 and CD28 coordinately facilitate T cell–APC interaction.

    Evidence fyn−/− mice with hCD2 transgene; CD2/CD28 double KO mice; Ca²⁺, MAPK, substrate phosphorylation assays

    PMID:10725714 PMID:11093170

    Open questions at the time
    • Whether fyn is required cell-autonomously for CD2 signaling in all T cell subsets unknown
    • Redundancy between CD2 and CD28 at the molecular signaling level not dissected
  12. 2001 High

    CD2 was shown to be inducibly recruited to lipid rafts upon engagement (requiring ectodomain conformational change), while p62dok was identified as a CD2-specific negative regulator that inhibits PLC-γ1 and ERK1/2 downstream of CD2 but not CD3.

    Evidence Lipid raft fractionation with cholesterol depletion and CD2 mutants; p62dok overexpression in Jurkat with Ca²⁺, PLC-γ1, ERK readouts

    PMID:11254695 PMID:11376005

    Open questions at the time
    • Raft recruitment kinetics in primary T cells not measured
    • Physiological relevance of p62dok regulation of CD2 not tested in vivo
  13. 2002 High

    Live-cell imaging revealed that CD2–CD58 engagement induces T cell polarization, uropod enrichment of CD2 (~100-fold), and scanning motility along APCs, establishing CD2 as a driver of T cell morphological dynamics during APC surveillance.

    Evidence Time-lapse DIC and immunofluorescence on living T cells, MLCK and integrin inhibition

    PMID:12032326

    Open questions at the time
    • Whether scanning motility depends on CD2 signaling vs. adhesion alone not separated
    • In vivo relevance of uropod CD2 enrichment unconfirmed
  14. 2006 High

    Biophysical dissection of CD2–CD58 bonds identified salt bridges as the primary determinants of tensile strength, and CD2 was found to promote membrane nanotube formation between NK cells and targets.

    Evidence Surface plasmon resonance and surface force apparatus with charge-reversal mutants; live-cell fluorescence of YTS NK cells with anti-CD2/CD58 blocking

    PMID:17172599 PMID:23112830

    Open questions at the time
    • Nanotube finding from a single NK cell line with overexpressed CD2
    • Whether nanotube formation is relevant to T cells not tested
  15. 2007 High

    Single-cell imaging showed CD2–CD58 interaction at the immunological synapse sustains antigen-induced Ca²⁺ signals and is required for PLC-γ1 recruitment and Tyr783 phosphorylation at the IS, establishing the biochemical convergence point of TCR and CD2 signaling.

    Evidence Single-cell Ca²⁺ imaging, IS immunofluorescence, PLC-γ1 phospho-assays, anti-CD58 blocking

    PMID:17220479

    Open questions at the time
    • Whether PLC-γ1 recruitment is via direct CD2 interaction or via LAT scaffolding not resolved
  16. 2008 High

    Nanoscale elongation of the CD2–CD48 intermembrane distance by 2–4 nm reduced adhesion 10-fold and reorganized the IS, revealing that precise intermembrane spacing is a critical biophysical parameter for CD2 function.

    Evidence Electron tomography, CD48 Ig-domain extension chimeras, primary T cell activation assays

    PMID:18826951

    Open questions at the time
    • Whether spacing effects apply identically to CD2–CD58 in human system not tested
  17. 2009 High

    Reconstituted bilayer and co-IP studies demonstrated that CD2 engagement alone nucleates TCR-ζ/Lck/LAT microclusters before TCR triggering, and that CD48 hierarchically shuttles LAT to the TCR/CD3 complex in a CD2-dependent manner.

    Evidence Single-molecule fluorescence on planar bilayers (Jurkat); co-IP with CD48 knockdown, LAT/Lck recruitment assays

    PMID:19398758 PMID:19494291

    Open questions at the time
    • Whether pre-formed CD2 microclusters are present in primary T cells in vivo unknown
    • Molecular basis of CD2-dependent LAT shuttling by CD48 not identified
  18. 2020 High

    Super-resolution imaging defined the 'CD2 corolla' at the outer immunological synapse where CD2–CD58 amplifies SFK/LAT/PLC-γ signaling by ~77% over central contacts; PD-1 invades this corolla to buffer signal amplification, providing a spatial mechanism for checkpoint inhibition of CD2-augmented TCR signaling.

    Evidence Super-resolution and confocal imaging with cellular and artificial APCs, genetic CD2 mutants, phospho-signaling measurements in primary T cells

    PMID:32929275

    Open questions at the time
    • Whether corolla disruption fully accounts for PD-1 inhibitory function unknown
    • Contribution of individual cytoplasmic tail motifs to corolla architecture incompletely mapped
  19. 2022 High

    FRET-based detection of cis CD2–CD48 interactions on the same T cell, combined with knockout epistasis showing T cell-intrinsic CD48 is required for TCR signaling, overturned the purely trans-interaction model and revealed that CD2 functions through both cis and trans ligand engagement.

    Evidence FRET in nonimmune cells, CD2/CD48 KO mice, CD2 knock-in tag mass spectrometry, PTK and cytotoxicity assays

    PMID:35930657

    Open questions at the time
    • Structural basis of cis vs. trans binding not determined
    • Whether cis interaction occurs with CD58 in human T cells not addressed
    • Relative signaling contribution of cis vs. trans engagement not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of CD2 corolla formation, the atomic mechanism by which cis CD2–ligand interactions promote TCR signaling, and how CD2 integrates with checkpoint receptors beyond PD-1 remain unresolved.
  • No high-resolution structure of CD2 in a cis complex
  • Mechanism of PD-1 invasion into the CD2 corolla not defined at molecular level
  • Role of CD2 in non-conventional T cell subsets (γδ, NKT) mechanistically uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1500931 Cell-Cell communication 4 GO:0005886 plasma membrane 1
Partners
CD247CD2BP2CD48CD58DOK1FYNLCKPTPRC
Complex memberships
TCR/CD3 signaling complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 LFA-3 (CD58) was identified as the physiological cell-surface ligand for CD2; LFA-3 cDNA encodes a phospholipid-linked (GPI-anchored) membrane protein whose extracellular domain shares homology with CD2, and CD2-LFA-3 interaction mediates T cell adhesion and conjugate formation. cDNA cloning, transient expression system, functional adhesion assays Nature High 3313052
1987 Binding of LFA-3 (T11 target structure) to CD2 on T cells provides one of the signals required for alternative pathway T cell activation, rendering resting T cells responsive to mitogenic anti-CD2 stimuli. Functional T cell activation assays with natural ligand and anti-CD2 mAbs Nature High 3102975
1989 The extracellular domain of CD2 is organized in two Ig-like domains; the NH2-terminal domain (exon 2, ~103 aa) is sufficient for LFA-3 binding with a Kd of ~0.4 µM, is resistant to proteolysis despite lacking intrachain disulfides, and ligand binding is not regulated by the cytoplasmic domain. Baculovirus and eukaryotic expression of recombinant CD2 fragments, circular dichroism, binding assays, truncation mutagenesis Immunological reviews / The Journal of experimental medicine High 2466941 2576417
1988 CD2 activation pathway is interdependent with CD3-Ti: Jurkat mutants lacking surface CD3-Ti fail to be activated through CD2 (no phosphoinositide turnover, Ca2+ mobilization, or IL-2 induction), and CD3-Ti re-expression restores CD2-mediated signaling. Jurkat mutant cell lines, DNA transfection reconstitution, phosphoinositide turnover, Ca2+ mobilization assays The EMBO journal High 2901344
1990 CD2 is physically associated with CD45 (T200, leukocyte common antigen) on the surface of human and mouse T lymphocytes, as demonstrated by chemical cross-linking and co-immunoprecipitation; CD45 tyrosine phosphatase activity may explain CD45's co-mitogenic effect with anti-CD2 antibodies. Chemical crosslinking, co-immunoprecipitation, co-precipitation from detergent lysates Nature / International immunology High 1970422 1980615
1991 CD2 adhesion function is constitutively active in resting T cells and is not upregulated by TCR stimulation, in contrast to LFA-1 whose adhesion is minimal at rest and rapidly augmented by TCR-mediated activation; this complementarity positions CD2 to initiate cell-cell contact before TCR engagement. Cell adhesion assays, PKC activation, cAMP manipulation, surface redistribution analysis European journal of immunology High 1672642
1991 Lateral mobility of LFA-3 and CD2 on membranes enhances adhesion strengthening; GPI-anchored LFA-3 (mobile) supports faster adhesion strengthening than transmembrane LFA-3 (immobile), and reducing CD2 mobility decreases adhesion strengthening rate. Reconstituted planar lipid bilayers, static and laminar flow adhesion assays, fluorescence recovery after photobleaching The Journal of cell biology High 1717480
1992 The CD3 zeta cytoplasmic domain is necessary and sufficient to couple CD2 to intracellular signal transduction (Ca2+ mobilization, protein tyrosine kinase activation, IL-2 secretion) in Jurkat cells lacking CD3-Ti, established by a CD8α/CD3ζ chimeric receptor transfection. Chimeric cDNA transfection into CD3-deficient Jurkat variants, Ca2+ measurement, PTK assay, IL-2 ELISA The Journal of experimental medicine High 1351920
1992 TCR-CD3 crosslinking rapidly increases CD2 avidity for CD58 (LFA-3); mutational analysis of the CD2 cytoplasmic domain shows the carboxyl-terminal asparagine is essential for avidity regulation but not for CD2-mediated signaling, defining structurally distinct functional domains; loss of avidity regulation impairs antigen-specific T cell responses. Mutational analysis of CD2 cytoplasmic domain, CD58 binding assays, antigen-specific T cell activation Proceedings of the National Academy of Sciences of the United States of America High 1353888
1992 N-glycosylation at Asn65 in domain 1 of CD2 is required for LFA-3 (CD58) binding and for recognition by adhesion-domain-specific anti-CD2 mAbs; high mannose oligosaccharides occupy Asn65; deglycosylation or Asn65Gln mutation abolishes CD2 adhesion function by destabilizing domain 1. Site-directed mutagenesis (Asn65Gln), enzymatic deglycosylation, binding assays, electrospray ionization-mass spectrometry The Journal of biological chemistry High 1385399
1993 CD2 binds CD48 via its NH2-terminal Ig domain in rats (and by analogy mice) with low affinity (Kd upper limit ~2.5 µM); binding does not require glycosylation of CD2 and is direct as shown by solution binding of bacterially expressed domain 1. Soluble chimeric CD48-CD4 protein, rosetting assay, sucrose gradient ultracentrifugation, bacterial expression of CD2 domain 1 European journal of immunology High 8099016
1994 CD2 forms a signaling complex with CD3 zeta chain and the Src-family tyrosine kinases p59fyn and p56lck in T lymphocytes, as identified by co-immunoprecipitation and in vitro kinase assays on CD2 immunoprecipitates; double immunofluorescence confirms the complex in living T cells. Co-immunoprecipitation, in vitro kinase assay, double indirect immunofluorescence with capping European journal of immunology High 7912674
1998 An intracellular adaptor protein CD2BP2 binds two PPPGHR proline-rich segments in the CD2 cytoplasmic tail via a novel 17-aa GYF motif; overexpression of the CD2BP2 binding domain in Jurkat cells enhances IL-2 production upon CD2 crosslinking but not TCR crosslinking. Yeast two-hybrid, NMR analysis, mutagenesis, Jurkat overexpression with IL-2 reporter Proceedings of the National Academy of Sciences of the United States of America High 9843987
1998 CD2 can signal through a p56lck-independent pathway involving Jun kinase activation; CD2-mediated IL-2 production occurs via JNK-dependent AP-1 activation in T cell lines lacking p56lck, whereas TCR-triggered activation requires p56lck. p56lck-deficient Jurkat cell lines, JNK kinase assays, AP-1/IL-2 promoter reporter assays The Journal of biological chemistry High 9727049
1999 CD2 sets quantitative activation thresholds; CD2-deficient T cells show a 3–10-fold rightward shift in antigen dose-response in vitro, impaired TCR triggering and Ca2+ flux at low antigen density; CD2 and LFA-1 adhesion pathways function additively. CD2 knockout mice crossed with TCR-transgenic mice, dose-response proliferation assays, conjugate formation, TCR triggering, Ca2+ flux measurement The Journal of experimental medicine High 10562314
2000 p59fyn is a critical Src-family PTK upstream in the CD2 signaling pathway; in fyn-/- mice expressing transgenic human CD2, CD2-triggered Ca2+ mobilization, MAPK activation and proliferation are markedly reduced, while TCR-triggered proliferation is unaffected; CD2 substrates regulated by fyn include PLC-γ1, Vav, PKC-θ, Dok, FAK and Pyk2. Transgenic human CD2 in fyn-/- mice, Ca2+ mobilization, MAPK assays, substrate phosphorylation analysis European journal of immunology High 11093170
2001 CD2 is inducibly recruited into lipid raft microdomains upon crosslinking by anti-CD2 mAbs or CD58 engagement; raft integrity is required for CD2-stimulated Ca2+ elevation and tyrosine phosphorylation; translocation requires ectodomain conformational change and is independent of TCR and cytoplasmic tyrosine phosphorylation; murine CD2 partitions constitutively into rafts via membrane-proximal cytoplasmic cysteines absent in human CD2. Lipid raft fractionation, cholesterol depletion, CD2 point mutation/deletion/chimeric constructs, Ca2+ and phosphorylation assays The Journal of biological chemistry High 11376005
2001 p62dok negatively regulates CD2 signaling in Jurkat T cells; overexpression of p62dok inhibits CD2-induced Ca2+ increase, PLC-γ1 activation, and ERK1/2 activation but not CD3/TCR-induced equivalents; CD2 (but not CD3) stimulation induces p62dok and RasGAP recruitment to the plasma membrane. Jurkat overexpression clones, Ca2+ flux, PLC-γ1 and ERK assays, subcellular fractionation Journal of immunology High 11254695
2002 CD2 engagement with CD58 induces T cell polarization and scanning motility along APC surfaces; CD2 molecules rapidly redistribute to the uropod with ~100-fold greater density versus the leading edge; CD2, TCR, and lipid rafts co-compartmentalize in the uropod, forming a 'presynapse'; scanning requires β-integrin function and myosin light chain kinase. Time-lapse DIC and immunofluorescence microscopy on living T cells, pharmacological inhibition Proceedings of the National Academy of Sciences of the United States of America High 12032326
2007 CD2-CD58 interaction at the immunological synapse augments and sustains antigen-induced Ca2+ increase in individual T cells and is required for PLCγ1 recruitment to the IS and phosphorylation of PLCγ1 at Tyr783; TCR and CD2 signals converge on PLCγ1 activation. Single-cell Ca2+ imaging, IS immunofluorescence, PLCγ1 phosphorylation assays, anti-CD58 blocking International immunology High 17220479
2008 Nanoscale increases in CD2-CD48 intermembrane spacing (by 2–4 nm achieved using elongated CD48 chimeras) reduce adhesion efficiency 10-fold and reorganize the immunological synapse; increased spacing causes eccentric CD2/TCR cluster formation and dramatically reduces T cell sensitivity. Electron tomography, confocal imaging, primary T cell activation assays, CD48 Ig-domain extension chimeras The Journal of biological chemistry High 18826951
2009 CD58 ligation of CD2 alone (without TCR activation) induces actin-dependent coalescence of signaling molecules (TCR-ζ, Lck, LAT) into plasma membrane microdomains in Jurkat cells on planar bilayers; CD2 and TCR initially colocalize in microdomains then partition into separate zones enabling synergistic signaling. Planar lipid bilayer model system, single-molecule fluorescence imaging, Jurkat T cells The Journal of cell biology High 19398758
2009 CD2 and GPI-anchored CD48 cooperate hierarchically in building the early TCR signalosome; CD2 associates with TCR/CD3 upon T cell activation irrespective of CD48 expression and recruits Lck; CD48 then shuttles the transmembrane adaptor LAT to the TCR/CD3 complex in a CD2-dependent manner. Co-immunoprecipitation, CD48 knockdown/knockout, LAT and Lck recruitment assays, IL-2 production Journal of immunology High 19494291
2020 CD2 localizes to the outer edge of the mature immunological synapse (the 'CD2 corolla') where it captures engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators; CD2-CD58 interactions in the corolla amplify phosphorylated SFK, LAT and PLC-γ signaling by ~77% versus central CD2-CD58; engaged PD-1 invades the CD2 corolla and buffers CD2-mediated TCR signal amplification; CD2 cytoplasmic tail motifs and copy number control corolla formation. Super-resolution/confocal imaging with cellular and artificial APC, genetic CD2 mutants, phospho-signaling measurements, primary T cell experiments Nature immunology High 32929275
2022 CD2 on T cells forms cis interactions with its ligand CD48 within the same T cell membrane (demonstrated by FRET); these T cell-intrinsic cis CD2-CD48 interactions are required for robust TCR signaling (protein tyrosine phosphorylation); CD48 is needed on T cells but not APCs for T cell activation (except during cytotoxicity where CD48 on APCs is also required); mass spectrometry of knock-in-tagged CD2 reveals association with TCR complex components and Lck. FRET in nonimmune cells, CD2/CD48 knockout mouse strains, mass spectrometry of CD2-KI tag IP, PTK phosphorylation assays, cytotoxicity assays Science immunology High 35930657
1992 CD59 (a GPI-anchored complement regulatory protein) functions as a second ligand for CD2 on T cells; CD2+ transfectants form rosettes with CD59-expressing CHO cells, blocked by anti-CD59 and anti-CD2 mAbs; 125I-CD59 binds specifically to CD2+ CHO cells; CD59 binding induces CD2R epitope expression. Rosette assays with transfected CHO cells, 125I-labeled CD59 binding, antibody blocking European journal of immunology Medium 1385156
1999 CD2 and CD3 independently associate with CD5 in T lymphocytes; CD5 is tyrosine phosphorylated after CD3 stimulation but dephosphorylated after CD2 crosslinking; this difference correlates with decreased SHP-1 activity in CD3 pathway versus enhanced SHP-1 after CD2 triggering, defining a regulatory link between CD2 and the phosphatase SHP-1 via CD5. Co-immunoprecipitation in CD3- and CD2-deficient cells, CD5 phosphorylation assays, SHP-1 activity assays Journal of immunology Medium 10510361
2000 Double knockout of CD2 and CD28 in mice causes profound defect in T cell activation by soluble anti-CD3 and antigen but not by immobilized anti-CD3, indicating CD2 and CD28 function coordinately to facilitate T cell-APC interactions for efficient TCR signaling. Double KO mice, T cell activation assays with soluble vs. immobilized stimuli Journal of immunology High 10725714
2006 CD2 promotes membrane nanotube formation between NK cells and susceptible target cells; CD2-CD58/48 receptor-ligand interaction is required for nanotube formation; CD2 localizes to nanotube tips; blocking LFA-1-ICAM or 2B4-CD48 interactions does not block nanotube formation, indicating specificity for CD2. YTS NK cell line with stable CD2 expression, anti-CD2/CD58 blocking, live-cell fluorescence microscopy, cytotoxicity assays PloS one Medium 23112830
2006 Salt bridges between CD2 and CD58 primarily determine tensile strength of the CD2-CD58 adhesive bond; specific charge mutations (D31A, K41A, K51A, K91A in CD2) reduce equilibrium binding affinity and adhesion strength, confirmed by surface plasmon resonance and surface force apparatus measurements. Site-directed mutagenesis, surface plasmon resonance, surface force apparatus adhesion measurement The Journal of biological chemistry High 17172599

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. Nature 742 3313052
1987 Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature 275 3102975
1990 Association of CD2 and CD45 on human T lymphocytes. Nature 184 1970422
1991 Influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2. The Journal of cell biology 173 1717480
2009 SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function. The EMBO journal 169 19262564
1989 The structural biology of CD2. Immunological reviews 161 2576417
2001 Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family. Journal of immunology (Baltimore, Md. : 1950) 159 11698418
1988 Interdependence of CD3-Ti and CD2 activation pathways in human T lymphocytes. The EMBO journal 153 2901344
1992 Development and function of T cells in mice with a disrupted CD2 gene. The EMBO journal 143 1358605
1986 T cell activation via CD2 [T, gp50]: the role of accessory cells in activating resting T cells via CD2. Journal of immunology (Baltimore, Md. : 1950) 137 2427570
2020 CD2 Immunobiology. Frontiers in immunology 121 32582179
2015 Rational evolution of Cd2+-specific DNAzymes with phosphorothioate modified cleavage junction and Cd2+ sensing. Nucleic acids research 111 25990730
2002 CS1, a novel member of the CD2 family, is homophilic and regulates NK cell function. Molecular immunology 110 12213321
2006 Proteome changes in Arabidopsis thaliana roots upon exposure to Cd2+. Journal of experimental botany 108 17075075
1988 Unusual expression of CD2 in sheep: implications for T cell interactions. European journal of immunology 106 2462499
1994 CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy. The Journal of experimental medicine 104 7525835
2020 A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals. Nature immunology 103 32929275
1991 Anti-CD2 antibodies induce T cell unresponsiveness in vivo. The Journal of experimental medicine 100 1682413
1999 CD2 sets quantitative thresholds in T cell activation. The Journal of experimental medicine 99 10562314
1992 CD59 molecule: a second ligand for CD2 in T cell adhesion. European journal of immunology 98 1385156
1992 Correlation of CD2 expression with PML gene breakpoints in patients with acute promyelocytic leukemia. Blood 97 1353379
2001 Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers. Cancer research 92 11691816
2009 The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. The Journal of cell biology 89 19398758
1998 Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation. Proceedings of the National Academy of Sciences of the United States of America 88 9843987
1991 Complementary roles for CD2 and LFA-1 adhesion pathways during T cell activation. European journal of immunology 80 1672642
1992 The CD3 zeta cytoplasmic domain mediates CD2-induced T cell activation. The Journal of experimental medicine 74 1351920
1993 The NH2-terminal domain of rat CD2 binds rat CD48 with a low affinity and binding does not require glycosylation of CD2. European journal of immunology 73 8099016
1970 Peritoneal macrophages in the immune response to SRBC in vitro. Immunology 73 4913802
2013 Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer. Journal of the National Cancer Institute 68 24273214
1989 Structural and binding analysis of a two domain extracellular CD2 molecule. The Journal of experimental medicine 67 2466941
2002 Studies on the interaction between Cd(2+) ions and DNA. Journal of inorganic biochemistry 64 12031800
2005 Clues to CD2-associated protein involvement in cytokinesis. Molecular biology of the cell 63 15800069
2003 CD2-associated protein and glomerular disease. Lancet (London, England) 62 14643126
2008 Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion and reorganize the immunological synapse. The Journal of biological chemistry 58 18826951
2000 Coordinate regulation of T cell activation by CD2 and CD28. Journal of immunology (Baltimore, Md. : 1950) 57 10725714
1992 A distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell responsiveness to antigen. Proceedings of the National Academy of Sciences of the United States of America 56 1353888
2012 Immunophenotyping in systemic mastocytosis diagnosis: 'CD25 positive' alone is more informative than the 'CD25 and/or CD2' WHO criterion. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 54 22222639
2001 Cloning, expression, and function of BLAME, a novel member of the CD2 family. Journal of immunology (Baltimore, Md. : 1950) 54 11313408
1992 N-glycosylation is required for human CD2 immunoadhesion functions. The Journal of biological chemistry 53 1385399
1995 Mammalian CD2 is an effective heterologous marker of the cell surface in Drosophila. Developmental biology 52 7729601
2005 CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. The Journal of biological chemistry 50 15951437
1992 Mechanism of peripheral T cell activation by coengagement of CD44 and CD2. Journal of immunology (Baltimore, Md. : 1950) 50 1381388
1991 CD2 can mediate TCR/CD3-independent T cell activation. Journal of immunology (Baltimore, Md. : 1950) 49 1674520
1988 Identification of a CD2- CD3+ T cell receptor-gamma+ peripheral blood lymphocyte subpopulation. Journal of immunology (Baltimore, Md. : 1950) 48 2895149
2001 Dynamic recruitment of human CD2 into lipid rafts. Linkage to T cell signal transduction. The Journal of biological chemistry 46 11376005
2003 Forced detachment of the CD2-CD58 complex. Biophysical journal 45 12668431
2002 CD2 molecules redistribute to the uropod during T cell scanning: implications for cellular activation and immune surveillance. Proceedings of the National Academy of Sciences of the United States of America 45 12032326
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