Search:
  • GENE_NAME : CD4

    CD_NAME : CD4

    DESC: CD4 antigen (p55)
    OTH_NAMES: none
    CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    OKT4 IgG2b  Ortho  eBioscience
    RPA-T4 IgG1k  Aversa  BD Biosciences
    RPA-T4 IgG1k  Aversa  BioLegend
    RPA-T4 IgG1k  Aversa  AbD Serotec
    RPA-T4 IgG1k  Aversa  eBioscience
  • CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    8F4 IgG1  Foster 
    13B8.2 IgG1  Mawas 
    16H5 IgG1  Emmrich 
    66.1 IgM Martin PJ
    91d6 IgG2a  Szer IS 
    94b1 IgG2a  Winchester 
    177F27 IgG1  Genetet 
    193-19 IgG1  Vilella 
    anti-T4 IgG2a  Amador 
    B-A1 IgG2a  Wijdenes 
    B-F5 IgG1  Wijdenes 
    BL4 IgG2a  Brochier 
    BL-TH4 IgM  Fiebig 
    BL-TH4/2 IgG  Fiebig 
    BW264/123 IgM  Kurrle 
    CD4-4D7 IgG2a  Knapp 
    CLB-T4/1 unknown  Tetteroo 
    CTAG-CD4, S3.5 IgG2a  Johnson 
    EDU-2 IgG  Vilella 
    F101-5 unknown  Poncelet 
    F101-69 (S-T4) unknown  Poncelet 
    F111-364 IgG1  Carriere 
    F142-63 IgG1  Carriere 
    G19-2 IgG1  Ledbetter 
    HIT4a IgG2b  Shen 
    HIT4b unknown  Shen 
    HP2/6 IgG2a  Sanchez-Madrid 
    ICO-86 IgG1  Baryshnikov 
    IP34 IgM  Bensussan 
    J5-19 IgG1  Pesando 
    L3 IgG1  Kikuchi 
    Leu-3a IgG1k  Evans 
    LT4 IgG1  Filatov 
    M-T151 IgG2a  Rieber 
    M-T310 IgG1  Rieber 
    M-T321 IgG1  Rieber 
    M-T404 IgG1  Rieber 
    M-T405 IgG1  Rieber 
    M-T406 IgG2a  Rieber 
    MEM-16 IgM  Horejsi 
    MEM-115 IgG2a  Horejsi 
    MEM-241 IgG1 Suchanek
    NU-Th/i IgG1  Yokoyama 
    O516 unknown  Boumsell 
    OKT4 IgG2b  Ortho  eBioscience
    OKT4A unknown  Connelly 
    Q4120 IgG1  More 
    R2B7 IgG2a  Foster 
    RPA-T4 IgG1k  Aversa  BD Biosciences
    T4 IgG1  Reinherz 
    T4 /7T4-6C1 IgM  Reinherz 
    T4 /12T4D11 IgG1  Reinherz 
    T4 /18T3A9 IgG1  Reinherz 
    T4 /19THY5D7 IgG2  Reinherz 
    T4a IgG2a  Yan Bai 
    TXU-5, B53 IgG1  Uckun 
    VIT4 unknown  Knapp 
    RPA-T4 IgG1k  Aversa  BioLegend
    RPA-T4 IgG1k  Aversa  AbD Serotec
    RPA-T4 IgG1k  Aversa  eBioscience
  • STRUCTURE


    CD4 is a type 1 transmembrane glycoprotein of the Ig superfamily. The extracellular domain contains 4 Ig-like domains and is followed by a transmembrane domain.1-3 CD4 has a cytoplasmic tail located in the N-terminal region with a CXCP motif for signalling.1,3

    1. Maddon PJ, Littman DR, Godfrey M, Maddon DE, Chess L, Axel R. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell. 1985;42:93-104.
    2. Harrison SC, Wang J, Yan Y, Garrett T, Liu J, Moebius U, Reinherz E. Structure and Interactions of CD4. Cold Spring Harb Symp Quant Biol. 1992;57:541-548.
    3. Bowers K, Pitcher C, Marsh M. CD4: a co-receptor in the immune response and HIV infection. Int J Biochem Cell Biol. 1997;29:871-5.
  • LIGANDS


    Extracellular

    MHC class II1, gp120 protein of HIV2, gp110 of Human T-lymphotropic virus type III and lymphadenopathy-associated virus3, gp174, IL-165-6 and protein-disulfide isomerase.7

    Intracellular associate molecules

    Focal adhesion kinase8, ACP339, lck10 and LAT.11

    1. Doyle C, Strominger JL. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987;330:256-9.
    2. McDougal JS, Kennedy MS, Sligh JM, Cort SP, Mawle A, Nicholson JK. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986;231:382-5.
    3. McDougal JS, Kennedy MS, Sligh JM, Cort SP, Mawle A, Nicholson JK. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986;231:382-5.
    4. Autiero M, Abrescia P, Guardiola J. Interaction of seminal plasma proteins with cell surface antigens: presence of a CD4-binding glycoprotein in humanseminal plasma. Exp Cell Res. 1991;197:268-71.
    5. Liu Y, Cruikshank WW, O'Loughlin T, O'Reilly P, Center DM, Kornfeld H. Identification of a CD4 domain required for interleukin-16 binding and lymphocyte activation. J Biol Chem. 1999;274:23387-95.
    6. Cruikshank WW, Greenstein JL, Theodore AC, Center DM. Lymphocyte chemoattractant factor induces CD4-dependent intracytoplasmic signaling in lymphocytes. J Immunol. 1991;146:2928-34.
    7. Gallina A, Hanley TM, Mandel R, Trahey M, Broder CC, Viglianti GA, Ryser HJ. Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry. J Biol Chem. 2002;277:50579-88.
    8. Garron ML, Arthos J, Guichou JF, McNally J, Cicala C, Arold ST. Structural basis for the interaction between focal adhesion kinase and CD4. J Mol Biol. 2008;375:1320-8.
    9. Zeitlmann L, Sirim P, Kremmer E, Kolanus W. Cloning of ACP33 as a novel intracellular ligand of CD4. J Biol Chem. 2001;276:9123-32.
    10. Veillette A, Bookman MA, Horak EM, Bolen JB. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988;55:301-8.
    11. Bosselut R, Zhang W, Ashe JM, Kopacz JL, Samelson LE, Singer A. Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction. J Exp Med. 1999;190:1517-26.

  • GENE_NAME : CD4

    CD_NAME : CD4

    CD4 is expressed on T helper cells and thymocytes.1 It is also expressed on dendritic cells2, NK3, monocytes4, macrophages4, neutrophils5 and eosinophils.6

    1. Ellmeier W, Haust L, Tschismarov R. Transcriptional control of CD4 and CD8 coreceptor expression during T cell development. Cell Mol Life Sci. 2013;70:4537-53.
    2. Patterson S, Gross J, English N, Stackpoole A, Bedford P, Knight SC. CD4 expression on dendritic cells and their infection by human immunodeficiency virus. J Gen Virol. 1995;76:1155-63.
    3. Bernstein HB, Plasterer MC, Schiff SE, Kitchen CM, Kitchen S, Zack JA. CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression and cell migration. J Immunol. 2006;177:3669-76.
    4. Kazazi F, Mathijs JM, Foley P, Cunningham AL. Variations in CD4 expression by human monocytes and macrophages and their relationships to infection with the human immunodeficiency virus. J Gen Virol. 1989;70:2661-72.
    5. Biswas P, Mantelli B, Sica A, Malnati M, Panzeri C, Saccani A, Hasson H, Vecchi A, Saniabadi A, Lusso P, Lazzarin A, Beretta A. Expression of CD4 on  human peripheral blood neutrophils. Blood. 2003;101:4452-6.
    6. Lucey DR, Dorsky DI, Nicholson-Weller A, Weller PF. Human eosinophils express CD4 protein and bind human immunodeficiency virus 1 gp120. J Exp Med. 1989;169:327-32.

  • GENE_NAME : CD4

    CD_NAME : CD4

    Through its interaction with MHC class II, CD4 is involved in thymic selection as well as Th cell activation and differentiation.1-3 Interaction with gp17 inhibits CD4/TCR-mediated T-cell apoptosis.4 CD4 is involved in IL16 T-cell migration and RANTES/eotaxin release from eosinophils.5-6 CD4 also modulates cytokine secretion and migration of NK cells.7

    1. Riberdy JM, Mostaghel E, Doyle C. Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+)  T cells in vivo. Proc Natl Acad Sci U S A. 1998;95:4493-8.
    2. Gay D, Maddon P, Sekaly R, Talle MA, Godfrey M, Long E, Goldstein G, Chess L, Axel R, Kappler J, et al. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987;328:626-9.
    3. Fowell DJ, Magram J, Turck CW, Killeen N, Locksley RM. Impaired Th2 subset development in the absence of CD4. Immunity. 1997;6:559-69.
    4. Gaubin M, Autiero M, Basmaciogullari S, Métivier D, Mis hal Z, Culerrier R, Oudin A, Guardiola J, Piatier-Tonneau D. Potent inhibition of CD4/TCR-mediated T  cell apoptosis by a CD4-binding glycoprotein secreted from breast tumor and seminal vesicle cells. J Immunol. 1999;162:2631-8.
    5. Lynch EA, Heijens CA, Horst NF, Center DM, Cruikshank WW. Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5. J Immunol. 2003;171:4965-8.
    6. Bandeira-Melo C, Sugiyama K, Woods LJ, Phoofolo M, Center DM, Cruikshank WW, Weller PF. IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling. J Immunol.  2002;168:4756-63.
    7. Bernstein HB, Plasterer MC, Schiff SE, Kitchen CM, Kitchen S, Zack JA. CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression and cell migration. J Immunol. 2006;177:3669-76.

  • GENE_NAME : CD4

    CD_NAME : CD4

    Cell marker

    Useful as a marker of lymphocytes T helper. CD4 cell counts are used to monitor progression in AIDS1 and could be used to identify immunocompromised patients susceptible to Pneumocystis jirovecii pneumonia.2

    1. Phillips AN, Lee CA, Elford J, Janossy G, Timms A, Bofill M, Kernoff PB. Serial CD4 lymphocyte counts and development of AIDS. Lancet. 1991;337:389-92.
    2. Messiaen PE, Cuyx S, Dejagere T, van der Hilst JC. The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review. Transpl Infect Dis. 2017;19.

     

    Therapeutic

    Ibalizumab (TNX-355) is a humanized monoclonal antibody against CD4 that has been studied for the treatment of HIV-1 infection.1 A phase III study of Ibalizumab has been successfully completed and is currently waiting for FDA approval.

    HuMax-CD4 (zanolimumab) is also a human monoclonal antibody against CD4. It has been studied for the treatment of cutaneous and non-cutaneous T-cell lymphoma2-3, mycosis fungoides4 and rheumatoid arthritis in phase II/III clinical trials.5 HuMax-CD4 was awarded Fast Tract candidate for the treatment of cutaneous T-cell lymphoma and Orphan drug for mycosis fungoides by the FDA.6

    Tregalizumab (BT-061) is a humanized non-depleting monoclonal antibody against CD4 which is able to activate regulatory T cells.7 Phase two studies of Tregalizumab have been performed in psoriasis8 and rheumatoid arthritis.9

    1. Reichert JM. Antibodies to watch in 2017. MAbs. 2017;9:167-181.
    2. ClinicalTrials.gov (NCT00877656) HuMax-CD4 in Non-Cutaneous T-Cell Lymphoma. U.S. National Institutes of Health.
    3. ClinicalTrials.gov (NCT00071071) Clinical Trial of HuMax-CD4, a New Drug to Treat Early Stage T-Cell Lymphoma in the Skin.U.S. National Institutes of Health.
    4. ClinicalTrials.gov (NCT00127881) Study of Human Monoclonal Antibody to Treat Mycosis Fungoides and Sezary Syndrome. U.S. National Institutes of Health.
    5. ClinicalTrials.gov (NCT00042406) Trial With HuMax-CD4 in Patients With Rheumatoid Arthritis Failing Treatment With Methotrexate and a TNF-alpha Blocker. U.S. National Institutes of Health.
    6. Reichert JM. Antibody-based therapeutics to watch in 2011. MAbs. 2011;3:76-99.
    7. König M, Rharbaoui F, Aigner S, Dälken B, Schüttrumpf J. Tregalizumab – A Monoclonal Antibody to Target Regulatory T Cells. Front Immunol. 2016 25;7:11.
    8. ClinicalTrials.gov (NCT01072383) Safety and Efficacy of Multiple Doses of BT061 in Patients With Moderate to Severe Chronic Plaque Psoriasis. U.S. National Institutes of Health.
    9. ClinicalTrials.gov (NCT01999192) Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis. U.S. National Institutes of Health.

  • GENE_NAME : CD4

    CD_NAME : CD4

    GENERAL_INFORMATION

    NCBI_NAME CD4
    NCBI_OTHER_NAME none
    SWISS_NAMES CD4_HUMAN
    DESC CD4 antigen (p55)

    LOCUS_INFO_LINKS

    HGNC_LOCUS_TAG: 1678
    ONLINE_MENDELIAN_INHERITANCE: 186940
    NCBI_HOMOLOGENE: 513
    NCBI_MAP: 12pter-p12
    NCBI_ENTRE_GENE_ENTRY: 920
    GENE_SIZE: 31231
    EN_GE_EN:
    MRNA_SEQ_LENGTH: 3084
    PRCORENC: 153 to 1529
    ENTREN: ENST00000011653
    PROTEIN_LENGTH_NCBI_REFSEQ: 459
    NCBI_REF_SEF_ENTRY: NP_000607 , 10835167
    PROTEIN_LENGTH_SWISPROT: 458
    ENSEMBLE_PROT_ENTRY: ENSP00000011653
    PR_MO_WEIGHT: 51110
    SWPROT_PROTEIN_ENTRY: CD4_HUMAN , P01730
    PR_SW_PR: 9.52
    IPI_NUMBER: IPI00003983
    NCBI_CONSV_DOMAINS: 10835167
    ENSM_NUMBER: P01730

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