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International Immunology Advance Access originally published online on June 13, 2006
International Immunology 2006 18(7):1179-1188; doi:10.1093/intimm/dxl052
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

T cell receptor cross-recognition of an HIV-1 CD8+ T cell epitope presented by closely related alleles from the HLA-A3 superfamily

Mathias Lichterfeld1, Katie L. Williams1, Stanley K. Mui1, Shivani S. Shah1, Bianca R. Mothe2, Alessandro Sette3, Arthur Kim1, Mary N. Johnston1, Nicole Burgett1, Nicole Frahm1, Daniel Cohen4, Christian Brander1, Eric S. Rosenberg1, Bruce D. Walker1,5, Marcus Altfeld1 and Xu G. Yu1

1 Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA, USA
2 Department of Biological Sciences, California State University, San Marcos, CA, USA
3 La Jolla Institute for Allergy and Immunology, San Diego, CA, USA
4 Fenway Community Health, Boston, MA, USA
5 Howard Hughes Medical Institute, Chevy Chase, MD, USA

Correspondence to: X. G. Yu; E-mail: xyu{at}partners.org

HLA-A3 and -A11 share similar peptide-binding motifs, however, it is unclear if promiscuous epitope presentation by HLA-A3 or HLA-A11 is associated with promiscuous TCR recognition. Here, we show that despite widespread cross-presentation of identical HIV-1 peptides in HIV-1-infected individuals expressing HLA-A3 or HLA-A11, peptides presented by HLA-A3 or HLA-A11 commonly exhibited clear immune distinctiveness with exclusive TCR recognition. Yet, using HLA-A3 and HLA-A11 tetramers for testing T cell cross-recognition of the HIV-1 Nef QK10 epitope, we observed in two study persons that specific CD8+ T cell populations were able to cross-recognize this peptide in the context of both HLA-A3 and HLA-A11. This cross-recognition was mediated by single cross-reactive TCRs, as shown by TCR sequencing in conjunction with TCR Vß chain immunostaining. In each cross-reactive cell population, multiple TCR ß chain variants were detected in the presence of only one TCR {alpha} chain variant. Thus, despite distinct TCR recognition of HLA-A3 or HLA-A11 presented HIV-1 peptides in the vast majority of cases, specific TCRs can cross-recognize their antigen in the context of both HLA-A3 and HLA-A11.

Keywords: cross-presentation, cross-recognition, cytotoxic T cells, HIV-1, HLA-A3 superfamily

Transmitting editor: R. Steinman


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