The effect of mutant β2-microglobulins on the conformation of HLA-B27 detected by antibody and by CTL

T. Fukazawa, E. Hermann, M. Edidin, J. Wen, F. Huang, H. Kellner, J. Floege, D. Farahmandian, K. M. Williams, D. T.Y. Yu

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish (US)
Pages (from-to)3543-3550
Number of pages8
JournalJournal of Immunology
Volume153
Issue number8
StatePublished - 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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