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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4283-4292. Prepublished online as a Blood First Edition Paper on February 12, 2008; DOI 10.1182/blood-2007-11-122622. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-11-122622v1 111/8/4283    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Wynn, K. K. Articles by Khanna, R. PubMed PubMed Citation Articles by Wynn, K. K. Articles by Khanna, R. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection Katherine K. Wynn1,2, Zara Fulton3, Leanne Cooper1, Sharon L. Silins1, Stephanie Gras3, Julia K. Archbold3, Fleur E. Tynan3, John J. Miles1,2, James McCluskey4, Scott R. Burrows1, Jamie Rossjohn3, and Rajiv Khanna1 1 Australian Centre for Vaccine Development and Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane; 2 School of Medicine, University of Queensland, Brisbane; 3 The Protein Crystallography Unit, Department of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash University, Clayton; and 4 Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia CD8+ T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)–specific CD8+ T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)–peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more "featureless" landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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