| 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 Behçet'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‐γ. 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. |
