Disease-associated human histocompatibility leukocyte antigen determinants in patients with seropositive rheumatoid arthritis. Functional role in antigen-specific and allogeneic T cell recognition

C. M. Weyand, J. J. Goronzy

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The susceptibility to develop seropositive rheumatoid arthritis (RA) has been linked to specific genomic polymorphisms within the HLA complex. Two different haplotypes have been associated with the disease, HLA-DR1 and HLA-DR4. To investigate the link between such phenotypic disease associations and potential immune mechanisms we used alloreactive and antigen-specific human T cell clones. Here we describe a panel of alloreactive T cell clones directed to polymorphic determinants encoded by the third hypervariable region (hvr) of the HLA-DR β1-chain. T cell determinants defined by these clones are shared among HLA-DR1, HLA-Dw4, HLA-Dw13, HLA-Dw14, and HLA-Dw15, and are frequent in a population of RA patients. To study the role of such disease-associated epitopes in antigen-restricted T cell recognition we generated T cell clones from RA patients specific for mycobacterial antigens, Epstein-Barr virus antigens, and tetanus toxoid. In all three antigenic systems T cell clones were restricted to either HLA-DR1 or HLA-DR4. These data suggest that the polymorphisms within the first and second hvr of the HLA-DR β1-chain are distinct in HLA-DR1 and HLA-DR4 and not associated with the disease are crucially involved in the recognition of antigens. Polymorphic determinants encoded by the third hvr are shared among disease-associated haplotypes and may function to mediate the interaction of alloreactive T cell receptor molecules with the HLA complex.

Original languageEnglish (US)
Pages (from-to)1051-1057
Number of pages7
JournalJournal of Clinical Investigation
Volume85
Issue number4
DOIs
StatePublished - 1990

Keywords

  • Epstein-Barr virus
  • HLA and disease association
  • HLA-DR β-chain
  • T cell clones
  • mycobacterial antigens

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Disease-associated human histocompatibility leukocyte antigen determinants in patients with seropositive rheumatoid arthritis. Functional role in antigen-specific and allogeneic T cell recognition'. Together they form a unique fingerprint.

Cite this