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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1553-1562. Prepublished online as a Blood First Edition Paper on June 19, 2009; DOI 10.1182/blood-2009-02-206193. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-206193v1 114/8/1553    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 Geldmacher, C. Articles by Koup, R. A. PubMed PubMed Citation Articles by Geldmacher, C. Articles by Koup, R. A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response Christof Geldmacher1, Ian S. Metzler2, Sodsai Tovanabutra3, Tedi E. Asher2, Emma Gostick4, David R. Ambrozak1, Constantinos Petrovas1, Alexandra Schuetz3,5, Njabulo Ngwenyama1, Gustavo Kijak3, Leonard Maboko5, Michael Hoelscher6, Francine McCutchan3, David A. Price2,4, Daniel C. Douek2, and Richard A. Koup1 1 Immunology Laboratory and 2 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; 3 US Military HIV Research Program, Rockville, MD; 4 Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom; 5 National Institute for Medical Research-Mbeya Medical Research Programme, Referral Hospital, Mbeya, Tanzania; and 6 Department of Infectious Diseases and Tropical Medicine, Klinikum of University of Munich, Munich, Germany Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting HLA class I molecule, CD8 T-cell responses elicited by subtype C exhibited largely comparable TL9 variant cross-recognition properties, expressed T-cell receptors that used almost exclusively the TRBV 12-3 gene, and selected for predictable patterns of viral variation within TL9. In contrast, subtype A elicited TL9-specific CD8 T-cell populations with completely different, more diverse TCRBV genes and did not select for viral variants. Moreover, TL9 variant cross-recognition properties were extensive in B81+ subjects but limited in B42+ subjects. Thus, minor viral and host genetic polymorphisms can dramatically alter the immunologic and virologic outcome of an epitope-specific CD8 T-cell response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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