6533b821fe1ef96bd127c441

RESEARCH PRODUCT

H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove.

subject

description

The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibilityI-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequencedH2-Ma, H2-Mb1, andH2-Mb2 genes from CIA-susceptible and-resistant mouse strains and identified four differentMa andMb2 alleles and three differentMb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share commonMa, Mb1, andMb2 alleles. In contrast,H2-M alleles designatedMa-III,Ma-IV,Mb1-III, andMb2-IV could be exclusively identified in the CIA-susceptibleH2 r andH2 q haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting “arthritogenic” epitopes to T lymphocytes.