The impact of a large and frequent deletion in the human TCR beta locus on antiviral immunity

Brennan, Rebekah M., Petersen, Jan, Neller, Michelle A., Miles, John J., Burrows, Jacqueline M., Smith, Corey, McCluskey, James, Khanna, Rajiv, Rossjohn, Jamie and Burrows, Scott R. (2012) The impact of a large and frequent deletion in the human TCR beta locus on antiviral immunity. Journal of Immunology, 188 6: 2742-2748. doi:10.4049/jimmunol.1102675


Author Brennan, Rebekah M.
Petersen, Jan
Neller, Michelle A.
Miles, John J.
Burrows, Jacqueline M.
Smith, Corey
McCluskey, James
Khanna, Rajiv
Rossjohn, Jamie
Burrows, Scott R.
Title The impact of a large and frequent deletion in the human TCR beta locus on antiviral immunity
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1872-7905
Publication date 2012-03
Sub-type Article (original research)
DOI 10.4049/jimmunol.1102675
Volume 188
Issue 6
Start page 2742
End page 2748
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2013
Language eng
Formatted abstract
The TCR plays a critical role in recognizing intracellular pathogens and initiating pathways leading to the destruction of infected cells by the immune system. Although genetic variability is known to greatly impact on the human immune system and the outcome of infection, the influence of sequence variation leading to the inactivation or deletion of TCR gene segments is unknown. To investigate this issue, we examined the CD8 + T cell response to an HLA-B7-restricted epitope ( 265RPHERNGFTVL 275) from the pp65 Ag of human CMV that was highly biased and frequently dominated by a public TCR β-chain encoded by the variable gene segment TRBV4-3. Approximately 40% of humans lack T cells expressing TRBV4-3 because of a 21.5-kb insertion/deletion polymorphism, but these individuals remain responsive to this epitope, using a diverse T cell repertoire characterized by private TCR usage. Although most residues within the bulged 11-mer peptide were accessible for TCR contact, the public and private TCRs showed distinct patterns of sensitivity to amino acid substitution at different positions within the peptide, thereby suggesting that the repertoire diversity generated in the absence of the dominant public TRBV4-3 + TCR could lead to better protection from viral escape mutation. Thus, variation in the size of the TRBV repertoire clearly contributes toward interindividual variability in immune responses and is presumably maintained in many ethnic groups to enhance the diversity of Ag-specific T cell responses.
Keyword Cell-Receptor Repertoire
Insertion/deletion Related Polymorphism
Maximum-Likelihood
Sequence Variation
Sjogrens-Syndrome
Antigen Receptor
Complex
Recognition
Infection
Selection
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 8 February 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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