Thymus-dependent (T) lymphocytes predominantly recognize antigens only when associated with products of the major histocompatibility complexes (MHC). This phenomenon is known as“genetic restriction”of the immune response. MHC Class II antigens restrict immunoregulatory T cells whereas Class I molecules determine the recognition by cytotoxic T cells or tumor cells and virus-infected cells. Genetic variations in cell-mediated and humoral responses to antigens have been related to variations in the first extracellular domain of Class II molecules.1The bulk of data relate to the mouse, but similar information relative to the human is rapidly emerging.