The arthritis-predisposing HLA-B27 consists of a heavy chain, a small peptide, and the monomorphic β2-microglobulin (β2-m). CTLs and a mAb, Ye- 2, which recognize the complex with specificities both for the heavy chain and for the peptide, are available. The β2-m is in noncovalent association with the heavy chain at multiple points and is exchangeable with free β2-m outside of the complex. The purpose of our experiments was to test whether mutant β2-m capable of modulating HLA-B27 activity could be created. Eighteen recombinant mutants of the human β2-m were experimentally generated. In 14 of these, mutations were at or near residues that are either contact residues or interface residues with the heavy chain. Relative to the parent β2-m, two-thirds of the mutants showed reduced ability to exchange into HLA-B27 complexes. However, at least four of them induced more than 80% decrease in Ye-2 Ab reactivity. Two mutants were able to induce a minor decrease in susceptibility to lysis by four CTL clones. One of the CTL clones was autoreactive. Two of the CTL clones were specific for HLA-B27 cells experimentally infected with arthritis-causing Yersinia enterocolitica. These results indicate that certain β2-m residues play an indirect role in peptide presentation, although they are not directly associated with the peptide residues.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - 1994|
ASJC Scopus subject areas
- Immunology and Allergy