MOLECULAR AND SEROLOGICAL ANALYSIS OF POLYMORPHISMS IN THE MURINE MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED PROTEASOME SUBUNITS, LMP-2 AND LMP-7

LMP-2 and LMP-7, gamma-interferon-inducible subunits of the 20S protea some, play an important role in antigen processing. To define the mole cular basis of their polymorphism, we sequenced Lmp-2 and Lmp-7 cDNA f rom nine different strains of mice. Three allelic variants of both LMP -2 and LMP-7 were found, but all of the polymorphism in LMP-7 is clust ered near the carboxyl terminus of the molecule. We confirmed the nucl eotide sequence changes at the protein level in both the unprocessed a nd processed forms of the molecules by analysis of specific anti-LMP-2 , anti-LMP-7 and anti-proteasome immunoprecipitates on two-dimensional PAGE gels. Interestingly, a single amino acid change at position 272 between LMP-7(b, d, q) and LMP-7(k, s, f, r, g7, cas4) from glycine to arginine dramatically affects its migration on SDS-PAGE gels, suggest ing the possibility of allele-specific posttranslational modification.