TCR USAGE BY HOMOCYSTEINE-SPECIFIC HUMAN CTL

We have recently demonstrated that homocysteine can modify HLA class I Ags and induce homocysteine-specific CTL (Hom-CTL) responses in human s, Here, we have investigated TCR usage by Hom-CTL from five patients with ankylosing spondylitis or reactive arthritis, TCR of HLA-A68-rest ricted Hom-CTL from two unrelated donors share the same TCR V alpha, V beta, and J beta gene segments (AV4, BV23, and BJ2S1, respectively) w ith similar third complementarity determining regions (CDR3) of the be ta-chains. Interestingly, the V alpha and V beta gene segments employe d by an HLA-B27-restricted Hom-CTL clone are also closely related to A V4 and BV23, indicating strong selection pressure for AV4, BV23, and r elated gene products in the homocysteine-specific TCR. An arginine or lysine residue frequently appeared at position alpha 93 in the CDR3 of the TCR alpha-chains from Hom-CTL restricted by HLA-A68 or -B8, This may suggest a potential salt bridge between the carboxyl group of homo cysteine and specific TCR. TCR usage by HLA-B27-restricted Hom-CTL fro m unrelated individuals appears to be less conserved, although two T c ell clones from one individual rearranged the same V gene segments wit h identical lengths of CDR3, Implications of these data for the molecu lar mechanisms for homocysteine modification of HLA Ags are also discu ssed.