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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-04, Vol.160 (8), p.3737-3742
Main Authors: Chilvers, Myo-Myo, Wordsworth, Paul, Stubbs, Andy, Gao, Xiao-Ming
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Arthritis, Reactive - immunology
Base Sequence
Clone Cells
DNA Primers - genetics
Genes, T-Cell Receptor alpha
Genes, T-Cell Receptor beta
HLA-A Antigens - metabolism
HLA-B27 Antigen - metabolism
HLA-B8 Antigen - metabolism
Homocysteine - immunology
Humans
In Vitro Techniques
Molecular Sequence Data
Polymerase Chain Reaction
Sequence Homology, Amino Acid
Spondylitis, Ankylosing - immunology
T-Lymphocytes, Cytotoxic - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.8.3737