CTL recognition of a bulged viral peptide involves biased TCR selection

Miles, John J., Elhassen, Diah, Borg, Natalie A., Silins, Sharon L., Tynan, Fleur E., Burrows, Jacqueline M., Purcell, Anthony W., Kjer-Nielsen, Lars, Rossjohn, Jamie, Burrows, Scott R., and McCluskey, James (2005) CTL recognition of a bulged viral peptide involves biased TCR selection. Journal of Immunology, 175 (6). pp. 3826-3834.

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MHC class I molecules generally present peptides of 8–10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related αβ TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.

Item ID: 45416
Item Type: Article (Research - C1)
ISSN: 1550-6606
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Funders: National Health and Medical Research Council of Australia (NHMRC), Roche Organ Transplantation Research Fund (ROTRF), Juvenile Diabetes Research Foundation (JDRF), Australian Research Council (ARC), Wellcome Trust (WT)
Date Deposited: 07 Sep 2016 05:22
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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