MHC class II Ab diabetogenic residue 57 Asp/non-Asp dimorphism influences T-cell recognition and selection

Immunogenetics
A N AntoniouP J Dyson

Abstract

Human and mouse major histocompatibility complex class II beta chain alleles associated with predisposition to type I diabetes often encode a non-charged residue at position 57 rather than the negatively charged aspartate residue characteristic of non-susceptible haplotypes. The mechanism(s) whereby this polymorphism promotes eventual pancreatic beta cell destruction is unclear. The type I diabetes-susceptible mouse strain NOD (H2(g7)) encodes serine at Ab position 57 and is one of the few mouse class II molecules not encoding aspartate at this position. To gain insight into the structural impact of this amino acid substitution and any influence it may have on T-cell selection, we assessed whether T-cell repertoires selected by diabetogenic class II (Ag7) are tolerant of mutant Ab (residues 56 and 57) H2-Ag7. We find that NOD mice mount an allogeneic response to skin grafts expressing mutant position 57 (serine to aspartate) Abg7; but not to grafts expressing mutant position 56 (histidine to proline) Abg7. Graft rejection correlates with the presence of CD4(+) T cells specific for the mutant H2-Ag7 heterodimer. Genetic analyses are consistent with Ab position 57 aspartate/non-aspartate dimorphism influencing peptide selection a...Continue Reading

Citations

Apr 8, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J A Todd
Jan 23, 1999·Current Opinion in Immunology·M McDuffie
Aug 21, 2010·Endocrinology and Metabolism Clinics of North America·Terri C ThayerClayton E Mathews
Apr 15, 2005·Molecular Immunology·Jonathan D SilkJulian Dyson
Apr 27, 2019·Annals of the New York Academy of Sciences·Tijana Martinov, Brian T Fife
Feb 24, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·M KrummelM M Davis
Jul 9, 1999·Diabetes/metabolism Research and Reviews·D W Gray
Jul 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S VendettiR Lechler
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S WinerH M Dosch
Mar 4, 1999·European Journal of Immunology·J G ChaiR Lechler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.