The roles of CD4 and CD8 in T cell activation.
CD4 and CD8 T cell surface molecules play a role in T cell recognition and activation by binding to their respective class II and class I major histocompatibility complex (MHC) ligands on an antigen presenting cell (APC). Though CD4 and CD8 are capable of binding to MHC molecules in the absence of the T cell receptor (TCR), increasing evidence suggests that they may primarily function by complexing with the TCR to form a 'co-receptor' for recognition of antigen-bound MHC. Using gene transfer studies we have demonstrated that CD4 and CD8 can augment antigen-induced IL-2 production through different mechanisms dependent on whether or not they can bind MHC independently of the TCR or complexed with the TCR. Under circumstances where CD4 and CD8 can bind to the same MHC ligand as the TCR, they potentiate antigen-induced IL-2 production maximally by a mechanism in large part dependent on their cytoplasmic tails. Enhancement of antigen-induced IL-2 production can also occur under circumstances where CD4 and CD8 bind on MHC ligand distinct from that recognized by the TCR. In this instance, the magnitude of this enhancement is not as great and appears (at least for CD8) to be independent of the cytoplasmic tail and the associated p56lck. The dependence of co-receptor function on the cytoplasmic tail of CD4 or CD8 may reflect the activity of the associated intracellular tyrosine kinase p56lck.(ABSTRACT TRUNCATED AT 250 WORDS)
Miceli
M C
MC
Department of Medicine, Stanford University Medical Center, CA 94305-5111.
Parnes
J R
JR
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011518:Proto-Oncogene Proteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)