The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miles, J. J.
Right arrow Articles by McCluskey, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miles, J. J.
Right arrow Articles by McCluskey, J.
Right arrowPubmed/NCBI databases
*Protein*Structure
The Journal of Immunology, 2005, 175: 3826-3834.
Copyright © 2005 by The American Association of Immunologists

CTL Recognition of a Bulged Viral Peptide Involves Biased TCR Selection1

John J. Miles2,*,{dagger}, Diah Elhassen2,{ddagger}, Natalie A. Borg§, Sharon L. Silins*, Fleur E. Tynan§, Jacqueline M. Burrows*, Anthony W. Purcell{ddagger}, Lars Kjer-Nielsen{ddagger}, Jamie Rossjohn§, Scott R. Burrows3,* and James McCluskey3,{ddagger}

* Cellular Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; {dagger} School of Population Health, University of Queensland, Herston, Australia; {ddagger} Department of Microbiology & Immunology, University of Melbourne, Parkville, Australia; and § Protein Crystallography Unit, Department of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia

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.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
L. M. Ebert, Y. C. Liu, C. S. Clements, N. C. Robson, H. M. Jackson, J. L. Markby, N. Dimopoulos, B. S. Tan, I. F. Luescher, I. D. Davis, et al.
A Long, Naturally Presented Immunodominant Epitope from NY-ESO-1 Tumor Antigen: Implications for Cancer Vaccine Design
Cancer Res., February 1, 2009; 69(3): 1046 - 1054.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Venturi, H. Y. Chin, T. E. Asher, K. Ladell, P. Scheinberg, E. Bornstein, D. van Bockel, A. D. Kelleher, D. C. Douek, D. A. Price, et al.
TCR {beta}-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV
J. Immunol., December 1, 2008; 181(11): 7853 - 7862.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Venturi, H. Y. Chin, D. A. Price, D. C. Douek, and M. P. Davenport
The Role of Production Frequency in the Sharing of Simian Immunodeficiency Virus-Specific CD8+ TCRs between Macaques
J. Immunol., August 15, 2008; 181(4): 2597 - 2609.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. L. La Gruta, P. G. Thomas, A. I. Webb, M. A. Dunstone, T. Cukalac, P. C. Doherty, A. W. Purcell, J. Rossjohn, and S. J. Turner
Epitope-specific TCR{beta} repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides
PNAS, February 12, 2008; 105(6): 2034 - 2039.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
P. Somma, G. Ristori, L. Battistini, S. Cannoni, G. Borsellino, A. Diamantini, M. Salvetti, R. Sorrentino, and M. T. Fiorillo
Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis
J. Leukoc. Biol., March 1, 2007; 81(3): 696 - 710.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
X. G. Yu, M. Lichterfeld, S. Chetty, K. L. Williams, S. K. Mui, T. Miura, N. Frahm, M. E. Feeney, Y. Tang, F. Pereyra, et al.
Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes
J. Virol., February 15, 2007; 81(4): 1619 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. Venturi, K. Kedzierska, D. A. Price, P. C. Doherty, D. C. Douek, S. J. Turner, and M. P. Davenport
Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination
PNAS, December 5, 2006; 103(49): 18691 - 18696.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. J. Miles, N. A. Borg, R. M. Brennan, F. E. Tynan, L. Kjer-Nielsen, S. L. Silins, M. J. Bell, J. M. Burrows, J. McCluskey, J. Rossjohn, et al.
TCR{alpha} Genes Direct MHC Restriction in the Potent Human T Cell Response to a Class I-Bound Viral Epitope
J. Immunol., November 15, 2006; 177(10): 6804 - 6814.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. H. Mealey, J.-H. Lee, S. R. Leib, M. H. Littke, and T. C. McGuire
A Single Amino Acid Difference within the {alpha}-2 Domain of Two Naturally Occurring Equine MHC Class I Molecules Alters the Recognition of Gag and Rev Epitopes by Equine Infectious Anemia Virus-Specific CTL
J. Immunol., November 15, 2006; 177(10): 7377 - 7390.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. K. Archbold, W. A. Macdonald, J. J. Miles, R. M. Brennan, L. Kjer-Nielsen, J. McCluskey, S. R. Burrows, and J. Rossjohn
Alloreactivity between Disparate Cognate and Allogeneic pMHC-I Complexes Is the Result of Highly Focused, Peptide-dependent Structural Mimicry
J. Biol. Chem., November 10, 2006; 281(45): 34324 - 34332.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
D. C. Young and D. B. Moody
T-cell recognition of glycolipids presented by CD1 proteins
Glycobiology, July 1, 2006; 16(7): 103R - 112R.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
L. Kjer-Nielsen, N. A. Borg, D. G. Pellicci, T. Beddoe, L. Kostenko, C. S. Clements, N. A. Williamson, M. J. Smyth, G. S. Besra, H. H. Reid, et al.
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
J. Exp. Med., March 20, 2006; 203(3): 661 - 673.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. E. Tynan, D. Elhassen, A. W. Purcell, J. M. Burrows, N. A. Borg, J. J. Miles, N. A. Williamson, K. J. Green, J. Tellam, L. Kjer-Nielsen, et al.
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation
J. Exp. Med., November 7, 2005; 202(9): 1249 - 1260.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.