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Human T-cell receptor V alpha gene polymorphism.

J A Wright1, L Hood, P Concannon

  • 1Virginia Mason Research Center, Seattle, WA 98101.

Human Immunology
|December 1, 1991
PubMed
Summary
This summary is machine-generated.

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Germline polymorphism in T-cell receptor (TCR) V alpha genes was investigated. While gene segment copy number variation was not found, sequence analysis revealed functionally relevant alleles, including a null allele, suggesting alternative mechanisms for TCR gene diversity.

Area of Science:

  • Immunogenetics
  • Molecular immunology
  • Human genetics

Background:

  • T-cell receptor (TCR) V alpha and V beta gene repertoire polymorphism can influence antigen response.
  • Previous studies indicated gene segment number variation in mice but not humans for V beta genes.
  • Human V alpha repertoire polymorphism at the gene segment level remained largely unexplored.

Purpose of the Study:

  • To investigate germline polymorphism in human T-cell receptor (TCR) V alpha gene segments.
  • To determine if variations in V alpha gene segment copy number exist in the human population.
  • To identify sequence-level polymorphisms within specific human V alpha gene segments.

Main Methods:

  • Surveyed 10 V alpha gene segment subfamilies (approx. 23 segments) in 120 unrelated individuals using hybridization.

Related Experiment Videos

  • Determined nucleotide sequences of eight V alpha 21 gene segments from seven unrelated individuals.
  • Analyzed sequences for polymorphic differences and identified distinct alleles.

    • Main Results:

    • No evidence of V alpha repertoire polymorphism based on gene segment copy number was found in the surveyed population.
    • Sequence analysis of V alpha 21 revealed three distinct alleles among the eight copies examined.
    • One identified V alpha 21 allele contained a frameshift mutation, leading to a premature stop codon (null allele).

    Conclusions:

    • Human T-cell receptor (TCR) V alpha gene segments do not appear to exhibit significant polymorphism in terms of copy number.
    • Functionally relevant germline polymorphism in human TCR V gene segments can occur at the sequence level, not just through gene duplication or deletion.
    • The discovery of a null allele suggests mechanisms beyond copy number variation contribute to the diversity of the human TCR repertoire.