Abstract
Spleen cells from BALB/c and C57BL/6 mice were cultured separately or together, and the biosynthetically labeled supernates were examined by two-dimensional polyacrylamide gel electrophoresis. Although there were no major labeled proteins in the mixed group that were not present in the separate cultures, there was a major low-molecular-weight protein that differed in charge in the two strains. This protein was identified as beta 2-microglobulin; it could be labeled with 125I on the cell surface by using the lactoperoxidase technique, was noncovalently attached to the H-2K molecule, and had the expected size and charge when compared with human beta 2-microglobulin. Both acidic and basic forms were present in (BALB/c X C57BL/6) F1 hybrids, suggesting codominant expression, although allelic exclusion was not ruled out. Either parental form could combine with one parental form of the H-2K molecule. The beta 2-microglobulin gene does not appear to be closely linked to either the H-2 or th immunoglobulin heavy-chain complexes. It is proposed that beta 2-microglobulin is an "effector subunit" of histocompatibility antigens and that its physiological role is to interact with a specific killing structure on the surface of cytolytic T lymphocytes and thereby initiate cell destruction.