Affinage

CD4

T-cell surface glycoprotein CD4 · UniProt P01730

Round 2 corrected
Length
458 aa
Mass
51.1 kDa
Annotated
2026-04-28
130 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD4 is a transmembrane glycoprotein of the immunoglobulin superfamily that functions as a co-receptor for MHC class II molecules to mediate T cell adhesion and as the primary receptor for HIV-1, while transducing activation signals through its constitutive association with the tyrosine kinase p56lck (PMID:2823150, PMID:3262426). Its V-like extracellular domain directly binds HIV-1 gp120, and this interaction induces a conformational change in gp120 that creates a high-affinity binding site for chemokine receptor co-receptors CCR5 or CXCR4, enabling viral membrane fusion and entry (PMID:8906795, PMID:9641677, PMID:8629022, PMID:8674119). CD4 surface expression is downregulated upon antigen stimulation via a PKC-dependent pathway and independently by HIV-1 Nef through a PKC-independent lysosomal degradation route that proceeds after dissociation of p56lck (PMID:3100638, PMID:2014052, PMID:7636966). CD4-null mice retain functional MHC class II-restricted helper T cells, demonstrating that CD4 enhances but is not absolutely required for helper lineage commitment or effector function (PMID:8367726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1984 High

    Identification of CD4 as the primary cell-surface receptor for HIV answered the fundamental question of how the virus achieves tropism for helper T cells and established the molecular basis of HIV entry.

    Evidence Antibody blocking of syncytia formation and pseudotype infection assays with 14 anti-CD4 monoclonal antibodies

    PMID:6096719

    Open questions at the time
    • Binding site on CD4 for HIV not yet mapped
    • Whether CD4 alone is sufficient for viral entry was unknown
  2. 1985 High

    Cloning and sequencing of CD4 cDNA revealed its immunoglobulin superfamily membership and multidomain architecture (V-like, J-like, transmembrane, cytoplasmic), providing the structural framework for understanding its receptor and adhesion functions.

    Evidence cDNA cloning, nucleotide sequencing, and deduced protein domain analysis

    PMID:2990730

    Open questions at the time
    • Three-dimensional structure not yet determined
    • Function of the cytoplasmic domain unknown
  3. 1986 High

    Direct biochemical demonstration that HIV gp120 binds to the CD4 molecule, with epitope mapping showing which CD4 epitope is occluded, resolved the molecular identity of the virus–receptor interaction and defined the gp120-binding region on CD4.

    Evidence Radioactive surface labeling and reciprocal co-immunoprecipitation with anti-CD4 and anti-HIV antibodies; parallel work showed gp120-CD4 interaction mediates syncytia and cytopathicity

    PMID:3001934 PMID:3016552

    Open questions at the time
    • Precise residues mediating the interaction not yet identified
    • Whether additional co-receptors are needed for viral entry remained unclear
  4. 1987 High

    Three concurrent advances established CD4's dual physiological and pathological roles: CD4 mediates MHC class II-dependent cell adhesion independent of TCR, gp120 residues 397–439 are critical for CD4 binding, and antigen stimulation downregulates CD4 via a PKC-dependent pathway linked to a CD3-CD4 multimolecular complex.

    Evidence Reconstitution of CD4-mediated adhesion to class II MHC+ cells in non-T cells; deletion/point mutagenesis of gp120; flow cytometry of T cell clones after antigen/PMA stimulation

    PMID:2441877 PMID:2823150 PMID:3100638

    Open questions at the time
    • Signaling mechanism downstream of CD4 not defined
    • Whether CD4 adhesion and TCR signaling are mechanistically coupled was unclear
  5. 1988 High

    Discovery that CD4 constitutively associates with p56lck via its cytoplasmic domain identified the first intracellular signaling partner of CD4 and explained how CD4 co-engagement amplifies TCR signaling, while soluble CD4 neutralization of HIV proved the extracellular domain alone is sufficient for gp120 binding.

    Evidence Reciprocal co-immunoprecipitation and cross-linking of CD4–p56lck from murine T cells; recombinant soluble CD4 binding and viral inhibition assays

    PMID:3257544 PMID:3262426

    Open questions at the time
    • Structural basis of CD4–p56lck interaction not resolved
    • Whether soluble CD4 could serve as a therapeutic in vivo was untested
  6. 1991 High

    Demonstration that HIV-1 Nef downregulates CD4 through a PKC-independent mechanism that does not require CD4 cytoplasmic serine phosphorylation established that HIV employs a distinct pathway from physiological CD4 internalization to evade immune recognition.

    Evidence Nef retroviral expression combined with CD4 triple serine-to-alanine mutagenesis, flow cytometry, and Western/Northern blot in lymphocytic lines

    PMID:2014052

    Open questions at the time
    • Endocytic sorting signals and adaptor proteins mediating Nef-induced CD4 degradation not yet identified
    • Whether Nef directly binds CD4 cytoplasmic tail was unresolved
  7. 1993 High

    CD4 knockout mice developing functional MHC class II-restricted T cells that control Leishmania infection revealed that CD4 is not absolutely required for helper T cell lineage commitment, redefining CD4 as an enhancer rather than an obligate determinant of class II-restricted immunity.

    Evidence CD4-null mice with Leishmania infection model, T cell subset analysis, cytokine assays, MHC restriction experiments

    PMID:8367726

    Open questions at the time
    • Quantitative contribution of CD4 to thymic positive selection efficiency not determined
    • Compensatory mechanisms in CD4-null mice not characterized
  8. 1995 Medium

    Myxoma virus-induced CD4 downregulation via a lysosomal, PKC-independent pathway with prior dissociation of p56lck provided a second viral system demonstrating that lysosomal targeting of CD4 is a convergent immune evasion strategy.

    Evidence Flow cytometry, NH4Cl lysosomal inhibition, staurosporine PKC inhibition, co-immunoprecipitation of p56lck–CD4, kinase assay

    PMID:7636966

    Open questions at the time
    • Whether the myxoma and HIV Nef pathways share sorting machinery was unknown
    • Viral protein responsible for triggering CD4 degradation not identified
  9. 1996 High

    The discovery that HIV-1 entry requires chemokine receptor co-receptors (CXCR4 for T-tropic and CCR5 for M-tropic strains) in addition to CD4, and that CD4 binding to gp120 induces a conformational change creating a high-affinity CCR5-binding site, resolved the long-standing puzzle of why CD4 expression alone was insufficient for infection and established the sequential receptor model of HIV entry.

    Evidence Functional reconstitution of HIV fusion/infection by co-expression of CD4 with fusin/CXCR4 or CCR5 in non-permissive cells; competitive binding assays showing CD4-induced enhancement of gp120–CCR5 affinity; antibody blocking of co-receptor engagement

    PMID:8629022 PMID:8674119 PMID:8906795 PMID:8906796

    Open questions at the time
    • Structural basis of the CD4-induced conformational change at atomic resolution not yet available
    • Kinetics of the sequential CD4→co-receptor engagement in membrane context not measured
  10. 1998 High

    The 2.5 Å crystal structure of the gp120 core complexed with CD4 revealed the atomic details of the CD4–gp120 interface, the conserved CCR5-binding surface exposed by CD4 engagement, and immune evasion mechanisms including glycan shielding, providing a structural foundation for understanding HIV tropism and vaccine design.

    Evidence X-ray crystallography of ternary gp120 core–CD4 two-domain fragment–Fab complex; complementary mutagenesis defining the conserved CCR5-binding element adjacent to V3

    PMID:9632396 PMID:9641677

    Open questions at the time
    • Full-length trimeric Env–CD4 complex structure not available
    • Dynamics of CD4-induced conformational rearrangement not captured by crystallography

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the CD4 cytoplasmic domain–p56lck interaction at atomic resolution, the precise endocytic sorting machinery that HIV Nef and other viral proteins co-opt to target CD4 for lysosomal degradation, and how CD4 co-engagement quantitatively modulates TCR signaling thresholds during thymic selection and peripheral activation.
  • No high-resolution structure of CD4 cytoplasmic domain–p56lck complex
  • Nef-recruited endocytic adaptor complex incompletely defined in the timeline
  • Quantitative contribution of CD4 to TCR signaling kinetics not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 5 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005764 lysosome 2
Pathway
GO:0005576 extracellular region 1
Partners
CCR5CXCR4LCK

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 CD4 (T4 antigen) is an essential and specific cell-surface receptor component required for HIV (HTLV-III/LAV) infection; anti-CD4 monoclonal antibodies blocked syncytia formation and pseudotype infection, and productive HIV infection markedly reduced CD4 surface expression, establishing CD4 as the primary viral receptor. Pseudotype virus infection assay, syncytia formation assay, antibody blocking with 14 anti-CD4 monoclonal antibodies, flow cytometry Nature High 6096719
1985 CD4 (T4) is an integral membrane glycoprotein belonging to the immunoglobulin supergene family, comprising an N-terminal V-like domain, a J-like region, a third extracellular domain, a transmembrane region homologous to MHC class II β-chains, and a highly charged cytoplasmic domain. cDNA cloning and nucleotide sequencing, deduced protein sequence analysis and structural comparison Cell High 2990730
1986 Binding of HIV gp110 (gp120) to the CD4 molecule on T4+ T cell surfaces was directly demonstrated; radioactive surface labeling and co-immunoprecipitation showed that HIV gp110 specifically coprecipitates with the 58K CD4 molecule, and virus binding blocked one CD4 epitope (OKT4A) but not another (OKT4), defining the gp120-binding domain on CD4. Radioactive surface labeling, co-immunoprecipitation with HIV antibodies and anti-CD4 monoclonal antibodies, blocking and absorption experiments Science High 3001934
1986 HIV envelope glycoprotein expression induces syncytia and cell death specifically in T4+ cells; syncytium formation requires interaction of envelope-expressing cells with neighboring cells bearing surface CD4 molecules, explaining HIV's specific cytopathic effect on CD4+ cells. Transfection of HIV env gene, syncytia formation assay in T4+ vs. T4- cell lines, antibody blocking Nature High 3016552
1987 CD4 directly mediates cell-cell adhesion by binding to MHC class II molecules; CV1 cells expressing recombinant CD4 adhered specifically to class II MHC-bearing B cells, and this adhesion was blocked by anti-class II and anti-CD4 antibodies, demonstrating CD4 as an adhesion molecule independent of T-cell receptor interactions. SV40-based expression vector, cell adhesion assay, antibody blocking with anti-CD4 and anti-class II MHC antibodies Nature High 2823150
1987 Antigenic stimulation of CD4+ T cell clones causes parallel downregulation of CD4 and CD3 surface expression to ~50% of constitutive levels; PMA-induced downregulation implicates protein kinase C in regulating CD4 expression, suggesting CD4 and CD3 are members of a multimolecular complex mediating T cell activation. Flow cytometry of T cell clones after antigen stimulation, PMA treatment, staurosporine inhibition Journal of Immunology Medium 3100638
1987 A critical region within gp120 (amino acids 397–439) is required for CD4 binding; deletion of 12 amino acids from this region abolished gp120-CD4 interaction, and a single amino acid substitution in this region significantly decreased binding. Recombinant gp120 production, in vitro mutagenesis (deletion and point mutations), binding assay to recombinant CD4 Cell High 2441877
1988 CD4 and CD8 T cell surface antigens are physically and functionally associated with the lymphocyte-specific tyrosine kinase p56lck; a large fraction of total cellular lck co-immunoprecipitates with CD4 or CD8, and antibody-mediated cross-linking of CD4 or CD8 specifically modulates p56lck, identifying p56lck as a CD4-associated signaling kinase. Co-immunoprecipitation with anti-CD4, anti-CD8, and anti-lck antibodies from murine T lymphocytes; antibody cross-linking experiments Cell High 3262426
1988 A soluble, secreted form of CD4 (sCD4) retains the structural and biological properties of cell-surface CD4, binds to HIV gp110, inhibits virus binding to CD4+ lymphocytes, and potently inhibits HIV infectivity, demonstrating the extracellular domain of CD4 is sufficient for gp120 interaction and viral neutralization. Recombinant protein expression, binding assay with HIV envelope glycoprotein, viral infectivity inhibition assay Nature High 3257544
1991 HIV-1 Nef protein downregulates cell-surface CD4 expression via a mechanism independent of serine phosphorylation and protein kinase C; Nef expression in CD4+ lymphocytic lines reduced surface CD4 without altering CD4 RNA or protein steady-state levels, and a CD4 triple serine-to-alanine mutant (non-phosphorylatable, phorbol ester-resistant) was still downregulated by Nef, indicating Nef acts through a distinct pathway. Retroviral vector expression of Nef, flow cytometry, Western blot, Northern blot, site-directed mutagenesis of CD4 serine residues Nature High 2014052
1993 CD4 is not strictly required for helper T cell lineage commitment or function; CD4-null mice develop a population of functional CD8- αβ TCR+ T cells that are MHC class II-restricted, produce IFN-γ in response to Leishmania antigens, and control infection, demonstrating CD4 glycoprotein is not absolutely necessary for class II-restricted helper T cell development or effector function. CD4 gene null mutation in mice, Leishmania infection model, T cell subset analysis, cytokine production assay, MHC restriction assays Science High 8367726
1995 Myxoma virus infection triggers CD4 downregulation in rabbit CD4+ T cells via a protein kinase C-independent, lysosomal pathway; early (but not late) viral gene expression was required, NH4Cl (lysosomal inhibitor) blocked CD4 degradation, and p56lck dissociated from CD4 prior to its lysosomal degradation without loss of total p56lck kinase activity. Flow cytometry, NH4Cl lysosomal inhibitor treatment, staurosporine PKC inhibitor treatment, Western blot, co-immunoprecipitation of p56lck with CD4, kinase activity assay Journal of Virology Medium 7636966
1996 A seven-transmembrane G protein-coupled receptor (fusin/CXCR4) serves as a cofactor for HIV-1 fusion and entry together with CD4; recombinant fusin enabled CD4-expressing nonhuman cells to support HIV-1 Env-mediated fusion and infection, and anti-fusin antibodies blocked fusion in normal CD4+ human cells, establishing that HIV-1 entry requires both CD4 and a chemokine receptor co-receptor. Functional cDNA expression cloning, cell fusion assay, antibody blocking, HIV-1 infection assay in non-permissive cells reconstituted with CD4 and fusin Science High 8629022
1996 CCR5 and CCR3 function as co-receptors for primary HIV-1 isolates together with CD4; CCR5 expressed with CD4 enabled cell lines resistant to primary HIV-1 to become infected, and CCR3 facilitated infection by a subset of viruses; co-receptor usage depended on the V3 region of gp120, explaining HIV-1 tropism. Transient transfection of chemokine receptors with CD4 in non-permissive cell lines, HIV-1 infection assays with primary isolates, CCR3 ligand (eotaxin) blocking Cell High 8674119
1996 CD4 binding to gp120 induces a conformational change in gp120 that creates a high-affinity binding site for CCR5; soluble CD4 dramatically increased the affinity of gp120 for CCR5, and a CD4-gp120 complex (but not CD4 alone or gp120 alone at low affinity) specifically interacted with CCR5 and competed with CCR5 natural ligands MIP-1α and MIP-1β. Competitive binding assay with radiolabeled CCR5 ligands, soluble CD4-gp120 complex formation, antibody neutralization blocking assays Nature High 8906795
1996 CD4 binding greatly increases the efficiency of the gp120-CCR5 interaction; competition assays on activated CD4+ T cells and CCR5+/CD4- cells showed CD4 is not absolutely required but greatly enhances gp120 binding to CCR5; neutralizing antibodies to V3 loop and CD4-induced epitopes on gp120 blocked gp120-CCR5 interaction without affecting gp120-CD4 binding. Competition binding assay using MIP-1β displacement on CD4+ T cells and CD4-negative CCR5+ cells, neutralizing antibody blocking experiments Nature High 8906796
1998 X-ray crystal structure of HIV-1 gp120 core in complex with a two-domain fragment of human CD4 (at 2.5 Å resolution) revealed a cavity-laden CD4-gp120 interface, a conserved chemokine receptor binding site exposed upon CD4 binding, evidence for a CD4-induced conformational change in gp120, and specific mechanisms for immune evasion including glycan shielding. X-ray crystallography at 2.5 Å resolution of ternary complex (gp120 core + CD4 two-domain fragment + neutralizing antibody Fab) Nature High 9641677
1998 A conserved gp120 structure adjacent to the V3 loop and containing CD4-induced epitopes is critical for CCR5 binding; gp120 mutants lacking this element failed to bind CCR5 despite retaining CD4 binding, and this element is shared across diverse primate immunodeficiency viruses, defining a conserved CCR5-binding surface on gp120 revealed by CD4 engagement. Site-directed mutagenesis of gp120, CCR5 binding assays, CD4 binding assays with recombinant mutant proteins Science High 9632396

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (New York, N.Y.) 3487 8629022
1984 The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 3268 6096719
1998 Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 2413 9641677
1996 The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 2053 8674119
2003 Antibody neutralization and escape by HIV-1. Nature 2019 12646921
1996 A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1669 8674120
2010 Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science (New York, N.Y.) 1511 20616233
1988 The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell 1497 3262426
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
2011 Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 1287 21849977
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1996 CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 1074 8906795
1986 Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science (New York, N.Y.) 1036 3001934
2010 Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science (New York, N.Y.) 1006 20616231
1996 Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. Journal of virology 988 8551569
1996 CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 974 8906796
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
1987 Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 879 2823150
1987 Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 876 2441877
2013 A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS pathogens 843 24068931
1986 Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 809 3016552
1988 In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. Journal of virology 766 3257102
2013 Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science (New York, N.Y.) 729 24179159
2011 Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 726 22113616
1998 A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science (New York, N.Y.) 726 9632396
1991 Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 716 2014052
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1985 The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 700 2990730
2005 Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 679 15616015
2008 Molecular architecture of native HIV-1 gp120 trimers. Nature 671 18668044
2003 Bacteriophage T4 genome. Microbiology and molecular biology reviews : MMBR 622 12626685
1988 A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature 552 3257544
2017 CD4 CTL, a Cytotoxic Subset of CD4+ T Cells, Their Differentiation and Function. Frontiers in immunology 355 28280496
2002 Clinical and biologic features of CD4(+)CD56(+) malignancies. Blood 317 11861268
2002 Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance. Journal of immunology (Baltimore, Md. : 1950) 286 12023351
1991 Systematic mutation of bacteriophage T4 lysozyme. Journal of molecular biology 281 1942069
1995 Studies on protein stability with T4 lysozyme. Advances in protein chemistry 272 7771320
2009 Plasticity of CD4(+) FoxP3(+) T cells. Current opinion in immunology 260 19500966
2023 CD4+ T cell memory. Nature immunology 245 37156885
1993 Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science (New York, N.Y.) 237 8367726
2003 Structure and morphogenesis of bacteriophage T4. Cellular and molecular life sciences : CMLS 199 14625682
2010 Morphogenesis of the T4 tail and tail fibers. Virology journal 193 21129200
1970 T4 endonuclease involved in repair of DNA. Proceedings of the National Academy of Sciences of the United States of America 180 5275382
2021 CD4+ T cells contribute to neurodegeneration in Lewy body dementia. Science (New York, N.Y.) 173 34648304
2010 Lessons from the lysozyme of phage T4. Protein science : a publication of the Protein Society 172 20095051
1987 Modulation of CD4 by antigenic activation. Journal of immunology (Baltimore, Md. : 1950) 157 3100638
1987 The subdivision of the T4 (CD4) subset on the basis of the differential expression of L-C/T200 antigens. The Journal of experimental medicine 133 2960772
2004 The bacteriophage T4 DNA injection machine. Current opinion in structural biology 125 15093831
2014 Structure and function of bacteriophage T4. Future microbiology 122 25517898
2018 Histone deacetylase function in CD4+ T cells. Nature reviews. Immunology 116 30022149
1975 Effect of salts and polyamines on T4 polynucleotide kinase. Biochemistry 114 164211
2001 Domain structure and mutational analysis of T4 polynucleotide kinase. The Journal of biological chemistry 112 11335730
1989 Enhancement of bacteriophage T4 late transcription by components of the T4 DNA replication apparatus. Science (New York, N.Y.) 107 2672335
2017 Engineering of Bacteriophage T4 Genome Using CRISPR-Cas9. ACS synthetic biology 106 28657724
1969 Selective translation of T4 template RNA by ribosomes from T4-infected Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 100 4904642
1976 Phosphorylation of double-stranded DNAs by T4 polynucleotide kinase. Biochemistry 96 178357
2010 Structure and assembly of bacteriophage T4 head. Virology journal 92 21129201
2014 TLR7 induces anergy in human CD4(+) T cells. Nature immunology 91 25401424
2016 Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase. Nature biotechnology 87 27617738
1975 Molecular and genetic recombination of bacteriophage T4. Annual review of genetics 87 1108766
1995 Modular organization of T4 DNA polymerase. Evidence from phylogenetics. The Journal of biological chemistry 86 7592876
1994 Tail length determination in bacteriophage T4. Virology 83 8122363
1992 Processive proofreading is intrinsic to T4 DNA polymerase. The Journal of biological chemistry 82 1629215
2024 CD4+ T cells in antitumor immunity. Trends in cancer 80 39242276
1993 Circular permutation of T4 lysozyme. Biochemistry 78 8241117
1980 RNA priming of DNA replication by bacteriophage T4 proteins. The Journal of biological chemistry 78 6243660
1988 Deletion formation in bacteriophage T4. Journal of molecular biology 76 3172217
1980 The rapid purification of T4 DNA ligase from a lambda T4 lig lysogen. The Journal of biological chemistry 76 6985906
1975 Kinetics and specificity of T4 polynucleotide kinase. Biochemistry 76 235284
2004 The functional domains of bacteriophage t4 terminase. The Journal of biological chemistry 74 15265872
2015 An atlas of mouse CD4(+) T cell transcriptomes. Biology direct 72 25886751
2010 Transcriptional control in the prereplicative phase of T4 development. Virology journal 71 21029433
2006 The DNA translocating ATPase of bacteriophage T4 packaging motor. Journal of molecular biology 67 16987527
1977 Enzyme associations in T4 phage DNA precursor synthesis. Proceedings of the National Academy of Sciences of the United States of America 67 198773
1982 Bacteriophage T4 late promoters: mapping 5' ends of T4 gene 23 mRNAs. The EMBO journal 65 6201352
2012 CD40L demethylation in CD4(+) T cells from women with rheumatoid arthritis. Clinical immunology (Orlando, Fla.) 64 22889643
2003 The tail lysozyme complex of bacteriophage T4. The international journal of biochemistry & cell biology 63 12467643
1995 Evolution of T4-related phages. Virus genes 61 8828153
1982 T4 late transcripts are initiated near a conserved DNA sequence. Nature 58 6287296
1974 Mutation to overproduction of bacteriophage T4 gene products. Journal of virology 58 4589857
1991 Supercoiled DNA-directed knotting by T4 topoisomerase. The Journal of biological chemistry 57 1657929
2023 CD4+ T cells aggravate hemorrhagic brain injury. Science advances 55 37285421
1988 DNA polymerase of bacteriophage T4 is an autogenous translational repressor. Proceedings of the National Academy of Sciences of the United States of America 55 3054876
1979 Purification of gene 41 protein of bacteriophage T4. The Journal of biological chemistry 55 376535
1973 Thymineless mutagenesis in bacteriophage T4. Genetics 54 4270369
2011 A promiscuous DNA packaging machine from bacteriophage T4. PLoS biology 53 21358801
2010 Transcription of the T4 late genes. Virology journal 52 21029432
1995 Multiple initiation mechanisms adapt phage T4 DNA replication to physiological changes during T4's development. FEMS microbiology reviews 48 7669352
2023 Effects of lactate on metabolism and differentiation of CD4+T cells. Molecular immunology 46 36621062
1984 Fluorescent labelling of tRNA and oligodeoxynucleotides using T4 RNA ligase. Nucleic acids research 46 6366740
1978 Polynucleotide kinase from a T4 mutant which lacks the 3' phosphatase activity. Nucleic acids research 46 205838
2017 NLRX1 Regulates Effector and Metabolic Functions of CD4+ T Cells. Journal of immunology (Baltimore, Md. : 1950) 45 28159898
1990 Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat. The Journal of experimental medicine 44 2147947
2019 The regulation of CD4+ T cells during malaria. Immunological reviews 43 31674682
2024 CD74 is a functional MIF receptor on activated CD4+ T cells. Cellular and molecular life sciences : CMLS 42 38992165
2015 Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm. DNA and cell biology 42 26667180
2010 T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology. Virology journal 41 21029435
2008 T4 endonuclease V: review and application to dermatology. Expert opinion on biological therapy 41 18476794
1998 DNA requirements in vivo for phage T4 packaging. Virology 41 9501053
1994 DNA helicase requirements for DNA replication during bacteriophage T4 infection. Journal of bacteriology 40 8132462
2023 TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells. Biology of sex differences 39 37723501
2012 Splint ligation of RNA with T4 DNA ligase. Methods in molecular biology (Clifton, N.J.) 39 23065567
2000 DNA polymerase of the T4-related bacteriophages. Progress in nucleic acid research and molecular biology 39 10697407
1998 The proofreading pathway of bacteriophage T4 DNA polymerase. The Journal of biological chemistry 38 9722519
1973 Transcription units in bacteriophage T4. Journal of virology 38 4591053
2021 Dynamic adoption of anergy by antigen-exhausted CD4+ T cells. Cell reports 37 33567282
2018 XNA ligation using T4 DNA ligase in crowding conditions. Chemical communications (Cambridge, England) 37 29872779
2018 Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs. Journal of immunology (Baltimore, Md. : 1950) 37 30030323
2016 Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells. Mediators of inflammation 35 27833268
2019 NFAT primes the human RORC locus for RORγt expression in CD4+ T cells. Nature communications 33 31619674
2009 Lack of TNFR2 expression by CD4(+) T cells exacerbates experimental colitis. European journal of immunology 33 19551899
1995 Myxoma virus induces extensive CD4 downregulation and dissociation of p56lck in infected rabbit CD4+ T lymphocytes. Journal of virology 33 7636966
2021 CD29 Enriches for Cytotoxic Human CD4+ T Cells. Journal of immunology (Baltimore, Md. : 1950) 32 34782446
2012 NFAT1 supports tumor-induced anergy of CD4(+) T cells. Cancer research 32 22865456
1997 ADP-ribosylation and early transcription regulation by bacteriophage T4. Advances in experimental medicine and biology 32 9193638
1983 Identification and biosynthesis of the bacteriophage T4 mot regulatory protein. The EMBO journal 32 6354709
1971 In vitro synthesis of deoxynucleotide kinase programmed by bacteriophage "T4-RNA. Proceedings of the National Academy of Sciences of the United States of America 32 4942183
2018 CD32 Ligation Promotes the Activation of CD4+ T Cells. Frontiers in immunology 31 30555482
1988 Head structure of bacteriophages T2 and T4. Journal of ultrastructure and molecular structure research 31 3198952
2020 miR-155 indicates the fate of CD4+ T cells. Immunology letters 30 32485191
2016 Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1. Nature communications 29 27670070
2021 Bacteriophage T4 Escapes CRISPR Attack by Minihomology Recombination and Repair. mBio 26 34154416
1979 The purification of nuclease-free T4-RNA ligase. Biochimica et biophysica acta 26 219895
2008 Regression supports two mechanisms of fork processing in phage T4. Proceedings of the National Academy of Sciences of the United States of America 25 18456838
1983 Fate of cloned bacteriophage T4 DNA after phage T4 infection of clone-bearing cells. Journal of molecular biology 25 6355485
1977 Phage T4-modified RNA polymerase transcribes T4 late genes in vitro. Proceedings of the National Academy of Sciences of the United States of America 25 271954
2009 RNA processing and decay in bacteriophage T4. Progress in molecular biology and translational science 24 19215770
1989 Rapid purification of overexpressed T4 DNA polymerase. Preparative biochemistry 24 2622873
2020 Structural basis of superinfection exclusion by bacteriophage T4 Spackle. Communications biology 23 33214665