MHC CLASS-II INTERACTION WITH CD4 MEDIATED BY A REGION ANALOGOUS TO THE MHC CLASS-I BINDING-SITE FOR CD8

INTERACTIONs between major histocompatibility complex (MHC) molecules and the CD4 or CD8 coreceptors have a major role in intrathymic T-cell selection 1. On mature T cells, each of these two glycoproteins is associated with a class-specific bias in MHC molecule recognition by the T-cell receptor. CD4+ T cells respond to antigen in association with MHC class II molecules and CD8+ T cells respond to antigen in association with MHC class I molecules. Physical interaction between the CD4/MHC class II molecules and CD8/MHC class I molecules has been demonstrated by cell adhesion assay 2-5, and a binding site for CD8 on class I has been identified 6,7. Here we demonstrate that a region of the MHC class II beta-chain beta-2-domain, structurally analogous to the CD8-binding loop in the MHC class I alpha-3 domain, is critical for function with both mouse and human CD4.