This Article Full Text (PDF) Other Versions of this Article: JVI.02564-06v1 81/10/5225    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 Malhotra, U. Articles by McElrath, M. J. Search for Related Content PubMed PubMed Citation Articles by Malhotra, U. Articles by McElrath, M. J.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.02564-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Enhanced Detection of HIV-1 Nef-Specific T-cells Recognizing Multiple Variants in Early HIV-1 Infection

Program in Infectious Diseases, Clinical Research Division, and the Statistical Center for HIV/AIDS Research & Prevention, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, WA, 98109, USA; Department of Medicine, Department of Microbiology, and Department of Laboratory Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA

^* To whom correspondence should be addressed. Email: uma{at}u.washington.edu.

	Abstract

Background: A preventive HIV vaccine will likely need to induce broad immunity that can recognize antigens expressed within circulating strains. To understand the potentially relevant responses that T-cell based vaccines should elicit, we examined the ability of T cells from early-infected persons to recognize a broad spectrum of potential T-cell epitopes (PTE) expressed by the products encoded by HIV-1 nef, which is commonly included in candidate vaccines. Methods: T cells were evaluated for IFN--secretion using two peptide panels: subtype B consensus (CON) peptides and a novel peptide panel providing 70% coverage of PTE in subtype B HIV-1 Nef. Results: Eighteen of 23 subjects' T cells recognized HIV-1 Nef. In one subject, Nef-specific T cells were detected with the PTE, but not the CON peptides. The greatest frequency of responses spanned Nef amino acids 65-103 and 113 -147, with multiple epitope variants being recognized. Detection of both the epitope domain number and response magnitude were enhanced using the PTE peptides. On average, we detected 2.7 epitope domains with the PTE versus 1.7 domains with CON peptides (P=0.0034). The average response magnitude was 2,169 SFC/10⁶ PBMC with the PTE versus 1,010 SFC/10⁶ PBMC with CON peptides (P=0.0046). Conclusions: During early HIV-1 infection, Nef-specific T cells capable of recognizing multiple variants are commonly induced; and these responses are readily detected with the PTE peptide panel. Our findings suggest that Nef responses induced by a given vaccine strain before HIV-1 exposure may be sufficiently broad to recognize most variants within subtype B HIV-1.

This article has been cited by other articles:

• Maness, N. J., Yant, L. J., Chung, C., Loffredo, J. T., Friedrich, T. C., Piaskowski, S. M., Furlott, J., May, G. E., Soma, T., Leon, E. J., Wilson, N. A., Piontkivska, H., Hughes, A. L., Sidney, J., Sette, A., Watkins, D. I. (2008). Comprehensive Immunological Evaluation Reveals Surprisingly Few Differences between Elite Controller and Progressor Mamu-B*17-Positive Simian Immunodeficiency Virus-Infected Rhesus Macaques. J. Virol. 82: 5245-5254 [Abstract] [Full Text]  
• Tagmyer, T. L., Craigo, J. K., Cook, S. J., Even, D. L., Issel, C. J., Montelaro, R. C. (2008). Envelope Determinants of Equine Infectious Anemia Virus Vaccine Protection and the Effects of Sequence Variation on Immune Recognition. J. Virol. 82: 4052-4063 [Abstract] [Full Text]  
• Turk, G., Gherardi, M. M., Laufer, N., Saracco, M., Luzzi, R., Cox, J. H., Cahn, P., Salomon, H. (2008). Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants. J. Virol. 82: 2853-2866 [Abstract] [Full Text]  
• Frahm, N., Kaufmann, D. E., Yusim, K., Muldoon, M., Kesmir, C., Linde, C. H., Fischer, W., Allen, T. M., Li, B., McMahon, B. H., Faircloth, K. L., Hewitt, H. S., Mackey, E. W., Miura, T., Khatri, A., Wolinsky, S., McMichael, A., Funkhouser, R. K., Walker, B. D., Brander, C., Korber, B. T. (2007). Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses. J. Immunol. 179: 6638-6650 [Abstract] [Full Text]