H2-M POLYMORPHISM IN MICE SUSCEPTIBLE TO COLLAGEN-INDUCED ARTHRITIS INVOLVES THE PEPTIDE BINDING GROOVE

The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and w ith as yet poorly defined regulatory molecules of the major histocompa tibility complex (MHC) class II antigen processing and presentation pa thway. H2-M molecules are thought to be involved in the loading of ant igenic peptides into the MHC class II binding cleft. We sequenced H2-M a, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles and three dif ferent Mb1 alleles defined by polymorphic residues within the predicte d peptide binding groove. Most CIA-resistant mouse strains share commo n Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-II I, Mn-IV, Mb1-III, and Mb2-IV could be exclusively identified in the C IA-susceptible H2(r) and H2(q) haplotypes, suggesting that allelic H2- M molecules may modulate the composition of different Cn peptides load ed onto MHC class II molecules, presumably presenting ''arthritogenic' ' epitopes T lymphocytes.