Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet's disease

Arthritis Rheum. 2004 Nov;50(11):3658-62. doi: 10.1002/art.20597.

Abstract

Objective: To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class I chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Behcet's disease (BD).

Methods: A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-gamma. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an HLA-B51-transfected B cell line in the presence of the MICA peptide.

Results: A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29%) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM.

Conclusion: HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity*
  • Behcet Syndrome / immunology*
  • Behcet Syndrome / physiopathology
  • Case-Control Studies
  • Female
  • HLA-B Antigens / analysis
  • HLA-B51 Antigen
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Peptide Fragments / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • HLA-B Antigens
  • HLA-B51 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • Peptide Fragments