PMID: 8943399Dec 1, 1996Paper

Modulation of HLA-DQ binding properties by differences in class II dimer stability and pH-dependent peptide interactions

The Journal of Immunology : Official Journal of the American Association of Immunologists
J BucknerG T Nepom

Abstract

Intermolecular interactions between peptides and class II molecules intracellularly are likely to be influenced by different pH conditions in different endosomal compartments. We compared the pH-dependent binding of peptides to HLA-DQ alleles 3.1 and 3.2, two well-studied human class II molecules with limited structural variability but different genetic associations with autoimmune diseases. Binding of the "promiscuous" binding peptide 34P3A as well as that of several allele-specific peptides were optimal for DQ3.2 at relatively acidic pH, compared with DQ3.1, with a pH optimum for DQ3.2 at pH 5.5 and for DQ3.1 at pH 6.5. A specific polymorphism at residue 57 of the DQ molecule accounted for some, but not all, of this difference. When the intrinsic stability of the class II dimer was assessed using partially denaturing gel electrophoresis after incubation at different pH, the DQ3.2 molecule demonstrated relative instability at neutral pH compared with DQ3.1, again suggesting a preference for peptide binding at relatively acidic conditions for HLA-DQ3.2. Interestingly, this preference for binding at acidic pH was not found for a class II-associated invariant chain peptide. Intrinsic alphabeta dimer stability and the pH optima fo...Continue Reading

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
W W KwokG T Nepom
The Journal of Immunology : Official Journal of the American Association of Immunologists
W W KwokF C Raymond
The Journal of Immunology : Official Journal of the American Association of Immunologists
Lynne S ArnesonAndrea J Sant
© 2021 Meta ULC. All rights reserved