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 CDS coreceptors have a major role in intrathymic T-cell selection¹. 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 CDS on class I has been identified^6,7. Here we demonstrate that a region of the MHC class IIβ-chain β₂ domain, structurally analogous to the CDS-binding loop in the MHC class I α₃domain, is critical for function with both mouse and human CD4.