This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.00708-07v1 81/14/7725    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Streeck, H. Articles by Altfeld, M. Search for Related Content PubMed PubMed Citation Articles by Streeck, H. Articles by Altfeld, M.

Recognition of a Defined Region within p24 Gag by CD8⁺ T Cells during Primary Human Immunodeficiency Virus Type 1 Infection in Individuals Expressing Protective HLA Class I Alleles

Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129,¹ Laboratoire d'Immunologie, Centre de Recherche du CHUM, Montreal, Quebec, Canada,² National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Darlinghurst, Australia,³ Department of Medicine, University of California, San Diego, San Diego, California 92093,⁴ McGill University, Division of Hematology and Immunodeficiency Service, Royal Victoria Hospital, Montreal, Quebec, Canada,⁵ Howard Hughes Medical Institute, Chevy Chase, Maryland 20815⁶

Received 3 April 2007/ Accepted 2 May 2007

Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8⁺ T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allele HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8⁺ T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P < 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles.

Published ahead of print on 9 May 2007.

This article has been cited by other articles:

• Streeck, H., Li, B., Poon, A. F.Y., Schneidewind, A., Gladden, A. D., Power, K. A., Daskalakis, D., Bazner, S., Zuniga, R., Brander, C., Rosenberg, E. S., Frost, S. D.W., Altfeld, M., Allen, T. M. (2008). Immune-driven recombination and loss of control after HIV superinfection. J. Exp. Med. 0: jem.20080281-8 [Abstract] [Full Text]  
• Schneidewind, A., Brockman, M. A., Sidney, J., Wang, Y. E., Chen, H., Suscovich, T. J., Li, B., Adam, R. I., Allgaier, R. L., Mothe, B. R., Kuntzen, T., Oniangue-Ndza, C., Trocha, A., Yu, X. G., Brander, C., Sette, A., Walker, B. D., Allen, T. M. (2008). Structural and Functional Constraints Limit Options for Cytotoxic T-Lymphocyte Escape in the Immunodominant HLA-B27-Restricted Epitope in Human Immunodeficiency Virus Type 1 Capsid. J. Virol. 82: 5594-5605 [Abstract] [Full Text]  
• Allen, T. M., Altfeld, M. (2008). Crippling HIV one mutation at a time. J. Exp. Med. 205: 1003-1007 [Abstract] [Full Text]  
• Loffredo, J. T., Bean, A. T., Beal, D. R., Leon, E. J., May, G. E., Piaskowski, S. M., Furlott, J. R., Reed, J., Musani, S. K., Rakasz, E. G., Friedrich, T. C., Wilson, N. A., Allison, D. B., Watkins, D. I. (2008). Patterns of CD8+ Immunodominance May Influence the Ability of Mamu-B*08-Positive Macaques To Naturally Control Simian Immunodeficiency Virus SIVmac239 Replication. J. Virol. 82: 1723-1738 [Abstract] [Full Text]  
• Geldmacher, C., Gray, C., Nason, M., Currier, J. R., Haule, A., Njovu, L., Geis, S., Hoffmann, O., Maboko, L., Meyerhans, A., Cox, J., Hoelscher, M. (2007). A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection. J. Virol. 81: 13809-13815 [Abstract] [Full Text]  
• Schneidewind, A., Brockman, M. A., Yang, R., Adam, R. I., Li, B., Le Gall, S., Rinaldo, C. R., Craggs, S. L., Allgaier, R. L., Power, K. A., Kuntzen, T., Tung, C.-S., LaBute, M. X., Mueller, S. M., Harrer, T., McMichael, A. J., Goulder, P. J. R., Aiken, C., Brander, C., Kelleher, A. D., Allen, T. M. (2007). Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication. J. Virol. 81: 12382-12393 [Abstract] [Full Text]