CD4; T-cell surface glycoprotein CD4; T-cell surface antigen T4/Leu-3

Function

• accessory protein for MHC class-II antigen/T-cell receptor interaction
• CD4+ T-cells are activated by simultaneous engagement of the T-cell receptor & CD4 by antigen-MHC II complexes on the surface of an antigen-presenting cell
• may regulate T-cell activation
• the signal is transduced by an associated tyrosine kinase lck-protein
• in vitro cross-linking of CD4 prior to engagement with the T-cell receptor, induces apoptosis
• induces the aggregation of lipid rafts
• palmitoylation & association with LCK contribute to the enrichment of CD4 in lipid rafts
• binds to P4HB/PDI

Structure

• contains 3 Ig-like C2-type domains (immunoglobulin-like)
• contains 1 Ig-like V-type domain (immunoglobulin-like)

Compartment

• cell membrane
• localizes to lipid rafts

Expression

• expressed with CD3
• thymocytes ~80-90%
• mature T-cells ~60-65%
  • T-helper & CD4/CD8+ thymocytes
• macrophages
• langerhans cells
• dendritic cells
• granulocytes

Pathology

• CD4 is recognized by HIV gp120
• part of P4HB/PDI-CD4-CXCR4-gp120 complex
• interacts with HIV-1 Envelope polyprotein gp160 & protein Vpu
• removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis to target it to lysosomal degradation
• cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, & sequesters CD4 in the endoplasmic reticulum

Laboratory

• a marker for T-helper cells

More general terms

• CD antigen
• adhesion receptor
• glycoprotein
• immunoglobulin superfamily protein

Additional terms

• CD4/CD8 ratio
• helper T cell (T4 lymphocyte, CD4+)
• HIV envelope glycoprotein gp120
• monocyte

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:920
• OMIM: https://mirror.omim.org/entry/186940
• UniProt: http://www.uniprot.org/uniprot/P01730.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=920