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We have recently demonstrated that homocysteine can modify HLA class I Ags and induce homocysteine-specific CTL (Hom-CTL) responses in humans. Here, we have investigated TCR usage by Hom-CTL from five patients with ankylosing spondylitis or reactive arthritis. TCR of HLA-A68-restricted Hom-CTL from two unrelated donors share the same TCR Valpha, Vbeta, and Jbeta gene segments (AV4, BV23, and BJ2S1, respectively) with similar third complementarity determining regions (CDR3) of the beta-chains. Interestingly, the Va and Vbeta gene segments employed by an HLA-B27-restricted Hom-CTL clone are also closely related to AV4 and BV23, indicating strong selection pressure for AV4, BV23, and related gene products in the homocysteine-specific TCR. An arginine or lysine residue frequently appeared at position alpha93 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 homocysteine and specific TCR. TCR usage by HLA-B27-restricted Hom-CTL from unrelated individuals appears to be less conserved, although two T cell clones from one individual rearranged the same V gene segments with identical lengths of CDR3. Implications of these data for the molecular mechanisms for homocysteine modification of HLA Ags are also discussed.

Type

Journal article

Journal

J Immunol

Publication Date

15/04/1998

Volume

160

Pages

3737 - 3742

Keywords

Amino Acid Sequence, Arthritis, Reactive, Base Sequence, Clone Cells, DNA Primers, Genes, T-Cell Receptor alpha, Genes, T-Cell Receptor beta, HLA-A Antigens, HLA-B27 Antigen, HLA-B8 Antigen, Homocysteine, Humans, In Vitro Techniques, Molecular Sequence Data, Polymerase Chain Reaction, Sequence Homology, Amino Acid, Spondylitis, Ankylosing, T-Lymphocytes, Cytotoxic