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 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 sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2r and H2q haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded into MHC class II molecules, presumably presenting "arthritogenic" epitopes to T lymphocytes.
Walter
W
W
Dept. of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
Loos
M
M
Maeurer
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001483:Base Sequence; D003094:Collagen / Q000276:immunology; D017931:DNA Primers; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D003094:Collagen