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TCR usage by homocysteine-specific human CTL

M M Chilvers1, P Wordsworth, A Stubbs

  • 1Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.

Journal of Immunology (Baltimore, Md. : 1950)
|April 29, 1998
PubMed
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Homocysteine modifies HLA class I antigens, inducing specific T cell responses. Certain T cell receptor gene segments are strongly selected in homocysteine-specific T cells, suggesting a conserved recognition mechanism.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Homocysteine can modify HLA class I antigens, triggering T cell responses.
  • T cell receptor (TCR) usage in these homocysteine-specific cytotoxic T lymphocytes (Hom-CTL) is largely uncharacterized.

Purpose of the Study:

  • Investigate TCR gene segment usage in Hom-CTL from patients with ankylosing spondylitis or reactive arthritis.
  • Explore potential molecular mechanisms of homocysteine modification of HLA antigens.

Main Methods:

  • Analyzed TCR Valpha, Vbeta, and Jbeta gene segments and CDR3 sequences of Hom-CTL.
  • Compared TCR usage across different HLA restrictions (HLA-A68, HLA-B27, HLA-B8).

Main Results:

  • Identified shared TCR Valpha, Vbeta, and Jbeta gene segments (AV4, BV23, BJ2S1) in HLA-A68-restricted Hom-CTL from unrelated donors.

Related Experiment Videos

  • Observed related V gene segments in an HLA-B27-restricted Hom-CTL clone, indicating selection for AV4, BV23, and related genes.
  • Found frequent arginine or lysine at TCR alpha-chain CDR3 position alpha93 for HLA-A68 or -B8 restricted Hom-CTL, suggesting a salt bridge interaction with homocysteine.

    • Conclusions:

    • Strong selection pressure exists for specific TCR gene segments (AV4, BV23) in homocysteine-specific T cell responses.
    • A potential salt bridge interaction may mediate homocysteine recognition by TCR.
    • TCR usage in HLA-B27-restricted Hom-CTL is less conserved but shows potential for specific rearrangements.