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Related Experiment Videos

A functionally significant allelic polymorphism in a T cell receptor V beta gene segment

S J Vessey1, J I Bell, B K Jakobsen

  • 1Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, Great Britain.

European Journal of Immunology
|July 1, 1996
PubMed
Summary

A specific T cell receptor (TCR) gene polymorphism impacts how TCRs recognize major histocompatibility complex (MHC)-peptide complexes. This finding highlights the functional significance of TCR variable gene diversity in immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • T cell receptors (TCRs) are crucial for adaptive immunity, recognizing peptide fragments presented by major histocompatibility complex (MHC) molecules.
  • Polymorphisms in TCR variable (V) genes can influence TCR specificity and function, but their precise impact on MHC-peptide recognition is not fully understood.

Purpose of the Study:

  • To investigate the effect of an allelic polymorphism in the BV1S1 gene segment on the recognition of MHC-peptide complexes by a specific TCR.
  • To determine the functional consequences of a specific amino acid substitution within the TCR on its binding affinity and T cell activation.

Main Methods:

  • Utilized RBL 2H3 cells engineered to express chimeric TCR-CD3 zeta receptors.
  • Generated an allelic variant of the BV1S1 gene segment using site-directed mutagenesis.

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  • Performed degranulation assays to assess the recognition of HLA-A2 HIV pol peptide-pulsed targets by engineered T cells.

    • Main Results:

    • Transfected RBL 2H3 cells expressing the wild-type TCR maintained the specificity of the parental cytotoxic T lymphocyte (CTL) clone.
    • The allelic variant BV1S1A1N1, with a histidine to glutamine substitution, resulted in cell surface expression but a complete loss of recognition for the target peptide.
    • This loss of recognition was observed despite successful cell surface expression of the chimeric receptor.

    Conclusions:

    • The studied polymorphism in the BV1S1 gene segment significantly affects TCR recognition of MHC-peptide complexes.
    • This finding supports current models of TCR-MHC-peptide interactions and underscores the functional importance of polymorphisms in TCRV genes for immune recognition.