Affinage

CD8A

T-cell surface glycoprotein CD8 alpha chain · UniProt P01732

Round 2 corrected
Length
235 aa
Mass
25.7 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD8A encodes the α chain of the CD8 co-receptor, a single-pass transmembrane glycoprotein with an immunoglobulin V-like extracellular domain that binds the α3 domain of MHC class I molecules to enhance TCR signaling on cytotoxic T lymphocytes (PMID:3871356, PMID:2784196, PMID:9177355). Its cytoplasmic tail recruits the Src-family kinase p56Lck through a zinc-dependent clasp structure, enabling Lck-mediated phosphorylation of CD3ζ and TCR signal transduction; superior coreceptor function requires the CD8αβ heterodimer, which partitions into lipid rafts—via CD8β palmitoylation in mice or heterodimer-driven ectodomain assembly in humans—concentrating Lck away from the phosphatase CD45 (PMID:2470098, PMID:14500983, PMID:10925291, PMID:17341584). Beyond classical coreceptor activity, the CD8αα homodimer binds the nonclassical MHC molecule TL to modulate intestinal intraepithelial lymphocyte responses, and CD8α engagement by soluble MHC-I or CEACAM5 can trigger FasL-mediated apoptosis or Lck activation leading to suppressor T cell function, respectively (PMID:11729321, PMID:10843658, PMID:24104458). CD8α also maintains peripheral T cell quiescence through interaction with PILRα; inducible loss of CD8α causes spontaneous activation and death of naïve and memory CD8+ T cells independently of antigen (PMID:35617401).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1985 High

    Establishing the molecular identity of the CD8 co-receptor: cloning and sequencing of CD8A revealed a transmembrane glycoprotein with an Ig V-like domain, defining the gene product that marks cytotoxic T lymphocytes.

    Evidence Gene transfer, subtractive hybridization, cDNA/genomic cloning, and sequencing in T cell lines

    PMID:3871356

    Open questions at the time
    • No binding partner or signaling function yet identified
    • Structure of the extracellular domain unknown
  2. 1989 High

    Two foundational functions were established simultaneously: CD8α binds the α3 domain of MHC class I (with a single residue at position 245 governing binding) and associates with p56Lck to phosphorylate CD3 subunits, linking CD8 to both antigen recognition and TCR signaling.

    Evidence Site-directed mutagenesis of HLA alleles with cell-cell binding assays; co-immunoprecipitation and in vitro kinase assays in T cells

    PMID:2470098 PMID:2784196

    Open questions at the time
    • Structural basis of CD8–MHC interaction unresolved
    • Mechanism of CD8α–Lck association unknown at atomic level
  3. 1992 High

    Crystal structure of the CD8α extracellular domain revealed an Ig V-like fold that homodimerizes as an Fv-like unit, providing the first atomic framework for understanding its MHC-binding surface.

    Evidence X-ray crystallography at 2.6 Å of soluble CD8α expressed in CHO cells

    PMID:1547508

    Open questions at the time
    • Structure of CD8αα in complex with MHC-I not yet available
    • No structural information on the CD8α–Lck interface
  4. 1997 High

    The co-crystal of CD8αα with HLA-A2/peptide at 2.7 Å resolved how CD8 engages MHC-I: the two CD8α subunits clamp a flexible loop of the α3 domain (residues 223–229) between their CDR-like loops, contacting both α2/α3 and β2m, with geometry that precludes binding a second MHC molecule.

    Evidence X-ray crystallography at 2.7 Å resolution

    PMID:9177355

    Open questions at the time
    • No structure of CD8αβ heterodimer with MHC-I
    • Functional difference between CD8αα and CD8αβ coreceptor activity unexplained structurally
  5. 2000 High

    The functional superiority of CD8αβ over CD8αα was mechanistically explained: CD8β palmitoylation drives heterodimer partitioning into lipid rafts where Lck is concentrated and CD45 is excluded, enabling efficient CD3ζ phosphorylation—a compartmentalization mechanism absent in the homodimer.

    Evidence Lipid raft fractionation, co-immunoprecipitation, phosphorylation assays, and CD8β cytoplasmic domain deletion mutants in T cell hybridomas (murine system)

    PMID:10925291

    Open questions at the time
    • Whether human CD8αβ uses the same palmitoylation-dependent mechanism was unresolved
    • Role of the CD8β extracellular domain in raft targeting not addressed
  6. 2001 High

    Discovery that CD8αα has a distinct ligand—the nonclassical MHC molecule TL—established a non-coreceptor function for the homodimer: CD8αα–TL binding on intestinal intraepithelial lymphocytes modulates TCR responses independently of classical MHC-I restriction.

    Evidence TL tetramer staining, binding assays, and functional T cell response assays

    PMID:11729321

    Open questions at the time
    • Structural basis of CD8αα–TL recognition unknown at this point
    • Downstream signaling consequences of TL engagement unclear
  7. 2003 High

    Three advances deepened the mechanistic picture: (i) the CD8α–Lck zinc clasp structure was solved by NMR, showing zinc-dependent co-folding of unstructured tails; (ii) ILTs were shown to compete with CD8 for MHC-I α3 binding with quantified affinities; (iii) soluble MHC-I ligation of CD8 was shown to upregulate FasL and induce apoptosis in both CD8+ T and NK cells.

    Evidence NMR solution structure of CD8α–Lck–Zn²⁺ complex; SPR-based competitive binding; apoptosis and FasL assays with blocking antibodies

    PMID:10843658 PMID:12594841 PMID:12853576 PMID:14500983

    Open questions at the time
    • Whether zinc clasp formation is regulated in vivo unknown
    • Physiological significance of soluble MHC–CD8 apoptotic signaling in immune regulation unclear
  8. 2007 High

    Species-specific mechanisms of CD8αβ raft targeting were delineated: in human T cells, heterodimer ectodomain assembly (not palmitoylation) drives raft localization, with CD8β cytoplasmic arginines contributing—contrasting the murine palmitoylation-dependent mechanism. Separately, genetic reconstitution confirmed that only CD8αβ (not CD8αα) provides coreceptor function for CD8-dependent TCRs.

    Evidence Chimeric CD8 protein analysis with lipid raft fractionation in human cells; retroviral TCR transfer into wild-type and CD8β-deficient primary mouse T cells

    PMID:17341584 PMID:17506031

    Open questions at the time
    • Structural basis for why CD8αα ectodomains exclude raft partitioning unknown
    • No structure of the human CD8αβ heterodimer
  9. 2013 Medium

    Two modulatory inputs onto the CD8 coreceptor axis were identified: CEACAM5 binds CD8α via its glycosylated N-domain to activate Lck and generate suppressor CD8+ T cells, while ART2.2-mediated ADP-ribosylation of CD8β impairs MHC-I tetramer binding and cytotoxicity in vivo.

    Evidence Co-immunoprecipitation with domain/glycosylation mutants, Lck kinase and T cell suppression assays (CEACAM5); NAD+ treatment, tetramer binding, and in vivo cytotoxicity in ART2-deficient mice (ADP-ribosylation)

    PMID:23575529 PMID:24104458

    Open questions at the time
    • CEACAM5–CD8α interaction validated only in one laboratory
    • Physiological relevance of ADP-ribosylation of CD8β to immune regulation in vivo needs broader confirmation
    • Structural basis of CEACAM5–CD8α binding unknown
  10. 2022 High

    A non-coreceptor homeostatic role for CD8α was established: inducible CD8α deletion causes spontaneous activation and death of naïve and memory CD8+ T cells, and PILRα was identified as a CD8α ligand whose disruption phenocopies this loss of quiescence—defining CD8α as a tonic quiescence signal independent of TCR-MHC interaction.

    Evidence Inducible CD8α knockout mice, flow cytometry phenotyping, co-immunoprecipitation identifying PILRα, functional disruption in mouse and human systems

    PMID:35617401

    Open questions at the time
    • Signaling pathway downstream of CD8α–PILRα interaction not characterized
    • Whether PILRα competes with MHC-I for CD8α binding unknown
    • Relevance to human autoimmune or immunodeficiency phenotypes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the CD8αβ heterodimer (no crystal or cryo-EM structure exists), how the CD8α–PILRα quiescence signal is transduced intracellularly, and whether the multiple non-coreceptor functions of CD8α (TL binding, CEACAM5 engagement, soluble MHC-induced apoptosis, PILRα-mediated quiescence) are integrated or context-exclusive.
  • No structure of CD8αβ heterodimer
  • Intracellular signaling downstream of CD8α–PILRα unknown
  • Functional hierarchy among multiple CD8α ligands in vivo unresolved

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 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2
Partners
B2MCD247CEACAM5LCKLILRB1PILRA
Complex memberships
CD8αα homodimerCD8αβ heterodimerCD8α–Lck zinc clasp complexTCR–CD3–CD8 signaling complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 CD8A (T8) encodes a transmembrane glycoprotein with an N-terminal immunoglobulin variable region-like domain; gene isolation and sequencing established it as a single-pass transmembrane protein defining a functional class of cytotoxic T lymphocytes. Gene transfer, subtractive hybridization, cDNA/genomic cloning, sequencing Cell High 3871356
1989 CD8A (and CD4) associates with the T cell-specific protein-tyrosine kinase p56lck; the CD8/p56lck complex phosphorylates CD3 complex subunits (γ, δ, ε, and ζ chains) at tyrosine residues, linking CD8A to TCR signaling. Co-immunoprecipitation, in vitro and in vivo radiolabeling, 2D-PAGE, in vitro kinase assay Proceedings of the National Academy of Sciences of the United States of America High 2470098
1989 CD8A binds to the α3 domain of MHC class I (HLA-A,B,C) molecules; a single amino acid at position 245 (alanine vs. valine) in the α3 domain determines CD8 binding, with valine abrogating binding. Cell-cell binding assay, site-directed mutagenesis of HLA alleles Nature High 2784196
1992 The extracellular domain of human CD8α forms an immunoglobulin variable domain fold and associates as Fv-like homodimers; only the N-terminal 114 amino acids form the structured domain visible in crystal structure. X-ray crystallography at 2.6 Å resolution of soluble CD8α fragment expressed in CHO cells Cell High 1547508
1997 Crystal structure of CD8αα homodimer in complex with HLA-A2/peptide at 2.7 Å: CD8αα binds one HLA-A2 molecule, contacting both the α2 and α3 domains of HLA-A2 and β2-microglobulin; a flexible loop of the α3 domain (residues 223–229) is clamped between the CDR-like loops of the two CD8α subunits; the binding mode precludes simultaneous binding of a second MHC molecule; no conformational change extends to the MHC/peptide surface. X-ray crystallography at 2.7 Å resolution Nature High 9177355
1999 Galectin-1-induced apoptosis in human T cells proceeds via segregation of CD45 and CD3 into distinct membrane microdomains (blebs with externalized phosphatidylserine) while CD7 and CD43 cluster separately; CD8 is not listed among the direct participants in galectin-1-induced death signaling. Flow cytometry, confocal microscopy, receptor redistribution assay Journal of immunology Low 10490978
2000 Soluble HLA-G1 triggers apoptosis in activated CD8+ T cells through the CD95/CD95L (Fas/FasL) pathway; the apoptotic effect is dependent on interaction with CD8 molecules, as blocking CD8 with various anti-CD8 mAbs prevents cell death. sHLA-G1 enhances CD95L expression on activated CD8+ T cells. Blocking antibody experiments, Western blotting for CD95L, CD95-Fc competitive inhibition, flow cytometry Journal of immunology Medium 10843658
2000 CD8β palmitoylation at its cytoplasmic tail allows CD8αβ heterodimer (but not CD8αα homodimer) to partition into lipid rafts. Raft localization concentrates CD8αβ with p56lck (nearly exclusively in rafts), enables CD8-mediated cross-linking to activate p56lck in a compartment lacking the phosphatase CD45, and allows p56lck to phosphorylate CD3ζ in rafts, inducing TCR signaling. Deletion of the CD8β cytoplasmic domain abolishes raft localization and p56lck association. Lipid raft fractionation, co-immunoprecipitation, phosphorylation assays, cytoplasmic domain deletion mutants, T cell hybridoma transfection system Journal of immunology High 10925291
2001 The nonclassical MHC class I molecule TL (thymus leukemia antigen) preferentially binds the CD8αα homodimer (not CD8αβ); TL tetramers specifically react with CD8αα-expressing cells including most intestinal intraepithelial lymphocytes. High-affinity CD8αα-TL binding modifies TCR-mediated responses to antigen presented by distinct MHC molecules, defining a novel regulatory mechanism distinct from classical coreceptor function. TL tetramer staining, binding assays, functional T cell response assays Science High 11729321
2003 ILT2 and ILT4 (inhibitory receptors) compete with CD8 for MHC class I binding at the α3 domain; surface plasmon resonance shows ILT2 binds classical MHCIs with Kd ~2–45 μM, binds HLA-G with 3–4 fold higher affinity than classical MHCI, and ILT2 binds with ~2–3 fold higher affinity than ILT4 to the same MHCI. ILT2/ILT4 effectively compete with CD8 for MHCI binding, suggesting ILT2 can modulate CD8+ T cell activation by blocking the CD8-MHC interaction. Surface plasmon resonance (SPR), competitive binding assays Proceedings of the National Academy of Sciences of the United States of America High 12853576
2003 Soluble classical HLA-A,-B,-C molecules (as well as sHLA-G1) induce apoptosis in both CD8+ T lymphocytes and CD8+ NK cells (which lack TCR) via CD8 ligation, leading to FasL upregulation, soluble FasL secretion, and Fas/sFasL-mediated cell death. Soluble HLA also inhibits EBV-specific CD8+ CTL cytotoxic activity through CD8 engagement. Apoptosis assays, FasL ELISA, blocking antibodies, purified soluble HLA molecules from serum and transfected cells European journal of immunology Medium 12594841
2003 The cytoplasmic tails of CD8α (and CD4) associate with the N-terminus of Lck through a zinc-mediated 'zinc clasp' structure. NMR solution structures of CD8α-Lck-Zn2+ ternary complex show that the unstructured cytoplasmic tails of CD8α and the Lck N-terminus co-fold in the presence of zinc into compact heterodimeric domains. The dileucine motif required for CD4 endocytosis is masked by Lck in the CD4-Lck complex; CD8α forms a similar but structurally distinct zinc clasp. NMR spectroscopy, solution structure determination of ternary complexes Science High 14500983
2007 CD8αβ heterodimer raft localization in human T cells is driven by assembly of CD8α and CD8β extracellular regions (not palmitoylation of human CD8α or CD8β per se). Formation of the CD8αβ heterodimer itself induces raft association: a non-raft CD8β chain combined with a non-raft CD8α chain yields raft-localized CD8αβ. Two CD8α extracellular regions (as in CD8αα) appear to preclude raft localization. Arginines in the CD8β cytoplasmic domain also contribute to raft localization. Lipid raft fractionation, chimeric CD8 proteins, palmitoylation analysis, transfection of human CD8 constructs The Journal of biological chemistry High 17341584
2007 CD8αα homodimers fail to provide coreceptor function for a CD8-dependent TCR; only CD8αβ heterodimers support antigen-specific cytotoxicity and IFN-γ production for a high-avidity CD8-dependent TCR clone. In CD8β-deficient T cells, only CD8-independent TCRs remain functional, demonstrating that CD8 dependence is TCR-intrinsic and requires the CD8β chain. Retroviral TCR gene transfer into wild-type and CD8β-deficient primary mouse T cells, antibody blocking, cytotoxicity assays, IFN-γ production European journal of immunology High 17506031
2013 CEACAM5 (gp180) interacts directly with CD8α through its N-domain, and this interaction activates CD8-associated Lck. CEACAM5 is the only CEACAM family member that interacts with CD8α; glycosylation of the CEACAM5 N-domain is critical for CD8α binding affinity and Lck activation. CEACAM5-activated CD8+ T cells acquire suppressor function (inhibiting CD4+ T cell proliferation) in the presence of IL-15 or IL-7. Co-immunoprecipitation, domain deletion/glycosylation mutants, Lck kinase activity assay, T cell suppression assay Mucosal immunology Medium 24104458
2013 ADP-ribosylation of CD8β (on murine CD8+ T cells) by ART2.2 using extracellular NAD+ modifies specific epitopes of CD8β, impairs binding of OVA:MHC-I tetramers to CD8, and reduces CD8+ T cell-mediated cytotoxicity in vivo. The modification is strictly ART2.2-dependent (absent in ART2-deficient T cells) and is reversed by anti-ART2.2 single-domain antibodies. NAD+ treatment, anti-CD8β antibody binding assays, MHC-I tetramer binding, in vivo cytotoxicity assay, ART2-deficient mice European journal of immunology Medium 23575529
2022 CD8α maintains peripheral CD8+ T cells in a physiologically quiescent state. Inducible deletion of CD8α causes both naïve and memory CD8+ T cells to spontaneously acquire activation phenotypes and die without antigen exposure. PILRα (paired immunoglobulin-like type 2 receptor alpha) was identified as a ligand for CD8α in both mice and humans; disruption of the CD8α-PILRα interaction breaks CD8+ T cell quiescence, defining a non-coreceptor function of CD8α in peripheral T cell homeostasis. Inducible CD8α knockout mice, flow cytometry phenotyping, co-immunoprecipitation/binding assays to identify PILRα as CD8α ligand, functional disruption experiments Science High 35617401

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 2257 31043744
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2019 TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 1241 31207603
2007 Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. The American journal of pathology 927 18156204
1999 Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes & development 914 10444591
2021 CD8+ T cell differentiation and dysfunction in cancer. Nature reviews. Immunology 770 34253904
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1998 The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 701 9790534
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1998 Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 585 9804427
2021 CD8+ T cell metabolism in infection and cancer. Nature reviews. Immunology 499 33981085
2011 Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer research 490 21430066
2020 The Roles of CD8+ T Cell Subsets in Antitumor Immunity. Trends in cell biology 482 32624246
1989 The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proceedings of the National Academy of Sciences of the United States of America 464 2470098
2003 Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proceedings of the National Academy of Sciences of the United States of America 448 12853576
2003 Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells. Science (New York, N.Y.) 422 14512632
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2018 Epigenetic control of CD8+ T cell differentiation. Nature reviews. Immunology 405 29379213
2021 CD8+ T Cell Exhaustion in Cancer. Frontiers in immunology 377 34354714
1997 Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature 376 9177355
2000 Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. Journal of immunology (Baltimore, Md. : 1950) 366 10843658
2016 S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature 346 27798602
1985 The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. Cell 320 3871356
2015 COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nature genetics 300 25894502
2003 Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. European journal of immunology 290 12594841
2003 Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms. Journal of molecular biology 287 12899833
2000 Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. The Journal of biological chemistry 274 11102443
1999 Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. Journal of immunology (Baltimore, Md. : 1950) 273 10490978
1989 Molecular biology and function of CD4 and CD8. Advances in immunology 257 2493728
1989 Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature 252 2784196
1992 Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution. Cell 246 1547508
2019 CD8+ T cell exhaustion. Seminars in immunopathology 243 30989321
2008 Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer research 209 18483277
2008 Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. The Journal of experimental medicine 209 18695005
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2003 A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science (New York, N.Y.) 202 14500983
2020 Sestrins induce natural killer function in senescent-like CD8+ T cells. Nature immunology 199 32231301
2001 T cell responses modulated through interaction between CD8alphaalpha and the nonclassical MHC class I molecule, TL. Science (New York, N.Y.) 198 11729321
2008 Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses. Proceedings of the National Academy of Sciences of the United States of America 193 18650384
2018 The epigenetic control of stemness in CD8+ T cell fate commitment. Science (New York, N.Y.) 188 29326266
2011 Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8α+ type. Journal of immunology (Baltimore, Md. : 1950) 180 21948982
2008 Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection. The Journal of clinical investigation 178 18398508
2022 Systemic vaccination induces CD8+ T cells and remodels the tumor microenvironment. Cell 169 36302380
2018 Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature 169 29849151
2017 NFATc1 controls the cytotoxicity of CD8+ T cells. Nature communications 167 28894104
2017 Tumor-derived exosomes induce CD8+ T cell suppressors. Journal for immunotherapy of cancer 157 28806909
2020 Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells. Cancer immunology research 155 33277233
2000 Essential role of CD8 palmitoylation in CD8 coreceptor function. Journal of immunology (Baltimore, Md. : 1950) 153 10925291
2005 Characterisation of salmon and trout CD8alpha and CD8beta. Molecular immunology 132 15829311
2011 The expression of CD8α discriminates distinct T cell subsets in teleost fish. Developmental and comparative immunology 131 21352850
2022 CD8+ T cell exhaustion and cancer immunotherapy. Cancer letters 126 36584935
2018 Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy. Cellular & molecular immunology 121 29400704
2012 Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunology and cell biology 115 23070399
2016 CD8+ T Lymphocyte Self-Renewal during Effector Cell Determination. Cell reports 111 27829149
1999 Role of CD8alpha+ and CD8alpha- dendritic cells in the induction of primary immune responses in vivo. Journal of leukocyte biology 109 10449161
2020 BATF3 programs CD8+ T cell memory. Nature immunology 107 32989328
2018 Regulation of CD8+ T Cells and Antitumor Immunity by Notch Signaling. Frontiers in immunology 98 29441071
2021 CXCR6 is required for antitumor efficacy of intratumoral CD8+ T cell. Journal for immunotherapy of cancer 97 34462326
2020 CD8+ T Cells in Atherosclerosis. Cells 94 33383733
2019 Endoplasmic Reticulum Stress Contributes to Mitochondrial Exhaustion of CD8+ T Cells. Cancer immunology research 86 30659052
2016 Starved and Asphyxiated: How Can CD8(+) T Cells within a Tumor Microenvironment Prevent Tumor Progression. Frontiers in immunology 86 26904023
2015 Molecular mechanisms of CD8(+) T cell trafficking and localization. Cellular and molecular life sciences : CMLS 86 25577280
2021 CD8+ Regulatory T Cell - A Mystery to Be Revealed. Frontiers in immunology 83 34484208
2020 The Identity of Human Tissue-Emigrant CD8+ T Cells. Cell 77 33306960
2019 Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells. Cell metabolism 75 31204281
2019 CD4+ and CD8a+ PET imaging predicts response to novel PD-1 checkpoint inhibitor: studies of Sym021 in syngeneic mouse cancer models. Theranostics 75 31754392
2012 Age-associated alterations in CD8α+ dendritic cells impair CD8 T-cell expansion in response to an intracellular bacterium. Aging cell 71 22862959
2016 RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells. The Journal of experimental medicine 70 27899443
2016 Hypoxia and antitumor CD8+ T cells: An incompatible alliance? Oncoimmunology 69 28123871
2019 The C1q Receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)1. Seminars in immunology 67 31744753
2012 Cross-dressed CD8α+/CD103+ dendritic cells prime CD8+ T cells following vaccination. Proceedings of the National Academy of Sciences of the United States of America 67 22802630
2018 Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells. Frontiers in immunology 62 29358941
2008 Emerging concepts in CD8(+) T regulatory cells. Current opinion in immunology 61 18406591
2009 Diversity in CD8(+) T cell differentiation. Current opinion in immunology 60 19497720
2023 Regulation of CD8+ T memory and exhaustion by the mTOR signals. Cellular & molecular immunology 58 37582972
2018 Costimulation through TLR2 Drives Polyfunctional CD8+ T Cell Responses. Journal of immunology (Baltimore, Md. : 1950) 56 30578304
2001 Mouse pre-immunocytes as non-proliferating multipotent precursors of macrophages, interferon-producing cells, CD8alpha(+) and CD8alpha(-) dendritic cells. European journal of immunology 56 11745359
2010 CD8+, CD8-, and plasmacytoid dendritic cell generation in vitro using flt3 ligand. Methods in molecular biology (Clifton, N.J.) 52 19941111
2021 CD8+ T cells inhibit metastasis and CXCL4 regulates its function. British journal of cancer 50 33795809
2017 Molecular Dissection of CD8+ T-Cell Dysfunction. Trends in immunology 50 28662970
2005 Properties of murine (CD8+)CD27- T cells. European journal of immunology 50 16220536
2022 Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood. Aging cell 49 35397197
2003 CD8alpha+ mouse spleen dendritic cells do not originate from the CD8alpha- dendritic cell subset. Blood 48 12649155
2022 Rgs16 promotes antitumor CD8+ T cell exhaustion. Science immunology 46 35622904
2015 Chaperone-like protein p32 regulates ULK1 stability and autophagy. Cell death and differentiation 44 25909887
2011 Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8α- dendritic cell subset. Journal of leukocyte biology 44 22147811
2000 Preferential induction of Th1 responses by functionally mature hepatic (CD8alpha- and CD8alpha+) dendritic cells: association with conversion from liver transplant tolerance to acute rejection. Transplantation 44 10910289
2021 CD8+ T Cell Responses during HCV Infection and HCC. Journal of clinical medicine 42 33801203
2020 Helpless Priming Sends CD8+ T Cells on the Road to Exhaustion. Frontiers in immunology 42 33123174
2021 CD8+ T-Cell Memory: The Why, the When, and the How. Cold Spring Harbor perspectives in biology 40 33648987
2007 CD8 Raft localization is induced by its assembly into CD8alpha beta heterodimers, Not CD8alpha alpha homodimers. The Journal of biological chemistry 40 17341584
2018 Cysteine-Reactive Free ISG15 Generates IL-1β-Producing CD8α+ Dendritic Cells at the Site of Infection. Journal of immunology (Baltimore, Md. : 1950) 38 29891555
2018 Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology 38 29981781
2016 MicroRNA-491 regulates the proliferation and apoptosis of CD8(+) T cells. Scientific reports 35 27484289
2017 Divide, Conquer, and Sense: CD8+CD28- T Cells in Perspective. Frontiers in immunology 32 28096804
2007 Unique functions of splenic CD8alpha+ dendritic cells during infection with intracellular pathogens. Immunology letters 32 17964665
2024 IL-4 drives exhaustion of CD8+ CART cells. Nature communications 29 39266501
2021 IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells. Immunology 28 34411293
2021 Epigenetics and CD8+ T cell memory. Immunological reviews 28 34923638
2020 Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms. Cellular oncology (Dordrecht, Netherlands) 28 32141029
2024 CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8+ T cells via JAK2/STAT3 pathway. Cell genomics 27 39317187
2023 KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans. Cell reports 27 36897779
1998 CD4+ CD8+ and CD8alpha+ beta- T lymphocytes in human small intestinal lamina propria. European journal of gastroenterology & hepatology 27 9855049
2007 CD8alpha/alpha homodimers fail to function as co-receptor for a CD8-dependent TCR. European journal of immunology 26 17506031
2014 Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives mitochondrial dysfunction. Cell reports 25 24746816
2025 Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes. The Journal of experimental medicine 23 39912921
2024 p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. International journal of biological sciences 23 38169635
2024 DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism. Cell discovery 23 38763950
2022 Arming a killer: mitochondrial regulation of CD8+ T cell cytotoxicity. Trends in cell biology 23 35753961
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