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 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.
Chilvers
M M
MM
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Wordsworth
P
P
Stubbs
A
A
Gao
X M
XM
D000595:Amino Acid Sequence; D016918:Arthritis, Reactive / Q000276:immunology; D001483:Base Sequence; D002999:Clone Cells; D017931:DNA Primers / Q000235:genetics; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D015234:HLA-A Antigens / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000378:metabolism; D015795:HLA-B8 Antigen / Q000378:metabolism; D006710:Homocysteine / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013167:Spondylitis, Ankylosing / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D017931:DNA Primers; D015234:HLA-A Antigens; D015796:HLA-B27 Antigen; D015795:HLA-B8 Antigen; D006710:Homocysteine