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: 3826-3834.


Author 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.
McCluskey, James
Title CTL recognition of a bulged viral peptide involves biased TCR selection
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2005-09
Sub-type Article (original research)
Volume 175
Issue 6
Start page 3826
End page 3834
Total pages 9
Editor R. Rich
Place of publication Bethesda, U.S.A.
Publisher American Association of Immunologists
Collection year 2005
Language eng
Subject C1
320299 Immunology not elsewhere classified
730102 Immune system and allergy
110704 Cellular Immunology
1107 Immunology
Abstract 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 alpha beta 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.
Keyword Immunology
T-cell-receptor
Epstein-barr-virus
Class-i
Structural Basis
Antigen Receptor
Binding-site
C-terminus
Repertoire
Complex
Diversity
Q-Index Code C1

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 65 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 05:49:51 EST