Interactions between MHC molecules and co-receptors of the TCR.
Genetic experiments indicate similarity between binding sites on MHC class I (MHCI) for CD8 and on MHCII for CD4, but the crystal structures of CD8/MHCI and CD4/MHCII complexes suggest critical differences between the interfaces in the two complexes. Biophysical analyses using ectodomains of co-receptors and MHC molecules demonstrate extremely fast kinetics and low-affinity interactions. Experiments with soluble multimeric MHC ligands suggest that CD4 and CD8 may differ in the mechanisms by which they promote the formation of ternary TCR/MHC/co-receptor complexes. Co-receptor-influenced duration of TCR signaling controls thymocyte selection. In naïve T cells, CD4/MHCII interactions may promote T-cell survival. Temporal and spatial analysis of TCR and CD4 co-clustering in the immunological synapse suggests that CD4 recruitment is regulated by the half-life of the initial TCR/MHCII complex. Diverse experimental systems have yielded conflicting data that have helped to formulate revised mechanistic models of co-receptor function.
König
Rolf
R
Department of Microbiology and Immunology and the Sealy Center for Molecular Science, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D011940:Receptor Aggregation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell