International Immunology, Vol 9, 43-51, Copyright © 1997 by Oxford University Press
B Reizis, M Eisenstein, J Bockova, S Konen-Waisman, F Mor, D Elias and IR Cohen
The MHC class II molecule of the non-obese diabetic (NOD) mice, I-Ag7, is
associated with susceptibility to autoimmune diabetes. To try to understand
the molecular basis of this association, we analyzed the peptide binding
properties and intracellular behavior of I-Ag7 in comparison with other I-A
haplotypes. We found that I-Ag7 molecules manifested normal intracellular
trafficking and lifespan, and a small but clearly detectable fraction of
I-Ag7 in the cells formed SDS- resistant compact dimers. The binding of an
antigenic reference peptide to I-Ag7 was stable and was accompanied by
compact dimer formation. Our analysis of the binding specificity of I-Ag7
revealed a peptide binding motif of nine amino acids with a degenerate
position at P1 and three conserved anchor positions: P4, P6 and P9. An
allele-specific preference for negatively charged residues was found at P9,
apparently due to the presence of the rare Ser residue at position 57 of
the I-Ag7 beta chain. These findings could have implications for the
mechanisms of MHC-mediated susceptibility to autoimmune diabetes in the NOD
mice.
ARTICLES
Molecular characterization of the diabetes-associated mouse MHC class II protein, I-Ag7
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
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