EXCESS BETA-2 MICROGLOBULIN PROMOTING FUNCTIONAL PEPTIDE ASSOCIATION WITH PURIFIED SOLUBLE CLASS-I MHC MOLECULES

T LYMPHOCYTES expressing alpha-beta-receptors recognize antigenic peptide fragments bound to major histocompatibility complex class I (ref. 1) or class II (ref. 2) molecules present on the surface membranes of other cells. Peptide fragments are present in the two available HLA crystal structures3,4 and recent data indicate that peptide is required for the stable folding of the class I heavy chain and maintenance of its association with the class I light chain beta-2-microglobulin (beta-2-m), at physiological temperature5-7. To explain how the exogeneous peptide used to create targets for cytotoxic cells bearing CD8 antigen1 could associate with apparently peptide-filled extracellular class I molecules, we hypothesized that stable binding of exogenous peptide to mature class I molecules reflects either the replacement of previously bound peptide during the well documented beta-2m exchange process8 or the loading of 'empty' class I heavy chains dependent on the availability of excess beta-2m. In either case, free beta-2m should enhance peptide-class I binding. Using either isolated soluble class I molecules or living cells, we show here that free purified beta-2m markedly augments the generation of antigenic complexes capable of T-cell stimulation.