HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McKinney, D. M. Articles by Newman, M. J. Search for Related Content PubMed PubMed Citation Articles by McKinney, D. M. Articles by Newman, M. J.

Recognition of Variant HIV-1 Epitopes from Diverse Viral Subtypes by Vaccine-Induced CTL¹

Denise M. McKinney^*, Rhonda Skvoretz^*, Brian D. Livingston^*, Cara C. Wilson, Michelle Anders, Robert W. Chesnut^*, Alessandro Sette^2,*, Max Essex, Vladimir Novitsky and Mark J. Newman^3,*

^* Epimmune, San Diego, CA 92121; University of Colorado Health Sciences Center, Divisions of Clinical Immunology and Infectious Disease, Denver, CO 80262; and Harvard School of Public Health, Department of Immunology and Infectious Disease, Boston, MA 02115

Recognition by CD8⁺ T lymphocytes (CTL) of epitopes that are derived from conserved gene products, such as Gag and Pol, is well documented and conceptually supports the development of epitope-based vaccines for use against diverse HIV-1 subtypes. However, many CTL epitopes from highly conserved regions within the HIV-1 genome are highly variable, when assessed by comparison of amino acid sequences. The TCR is somewhat promiscuous with respect to peptide binding, and, as such, CTL can often recognize related epitopes. In these studies, we evaluated CTL recognition of five sets of variant HIV-1 epitopes restricted to HLA-A*0201 and HLA-A*1101 using HLA transgenic mice. We found that numerous different amino acid substitutions can be introduced into epitopes without abrogating their recognition by CTL. Based on our findings, we constructed an algorithm to predict those CTL epitopes capable of inducing responses in the HLA transgenic mice to the greatest numbers of variant epitopes. Similarity of CTL specificity for variant epitopes was demonstrated for humans using PBMC from HIV-1-infected individuals and CTL lines produced in vitro using PBMC from HIV-1-uninfected donors. We believe the ability to predict CTL epitope immunogenicity and recognition patterns of variant epitopes can be useful for designing vaccines against multiple subtypes and circulating recombinant forms of HIV-1.

This article has been cited by other articles:

				C. C. Wilson, M. J. Newman, B. D. Livingston, S. MaWhinney, J. E. Forster, J. Scott, R. T. Schooley, and C. A. Benson Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy Clin. Vaccine Immunol., June 1, 2008; 15(6): 986 - 994. [Abstract] [Full Text] [PDF]

				H. O. Peters, M. G. Mendoza, R. E. Capina, M. Luo, X. Mao, M. Gubbins, N. J. D. Nagelkerke, I. MacArthur, B. B. Sheardown, J. Kimani, et al. An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1 gag in the Pumwani Sex Worker Cohort J. Virol., February 15, 2008; 82(4): 1980 - 1992. [Abstract] [Full Text] [PDF]

				L. E. Valentine, S. M. Piaskowski, E. G. Rakasz, N. L. Henry, N. A. Wilson, and D. I. Watkins Recognition of Escape Variants in ELISPOT Does Not Always Predict CD8+ T-Cell Recognition of Simian Immunodeficiency Virus-Infected Cells Expressing the Same Variant Sequences J. Virol., January 1, 2008; 82(1): 575 - 581. [Abstract] [Full Text] [PDF]

				A. A. Chentoufi, X. Zhang, K. Lamberth, G. Dasgupta, I. Bettahi, A. Nguyen, M. Wu, X. Zhu, A. Mohebbi, S. Buus, et al. HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D J. Immunol., January 1, 2008; 180(1): 426 - 437. [Abstract] [Full Text] [PDF]

				J. T. Loffredo, B. J. Burwitz, E. G. Rakasz, S. P. Spencer, J. J. Stephany, J. P. Giraldo Vela, S. R. Martin, J. Reed, S. M. Piaskowski, J. Furlott, et al. The Antiviral Efficacy of Simian Immunodeficiency Virus-Specific CD8+ T Cells Is Unrelated to Epitope Specificity and Is Abrogated by Viral Escape J. Virol., March 15, 2007; 81(6): 2624 - 2634. [Abstract] [Full Text] [PDF]

				S. M. Mueller, B. Schaetz, K. Eismann, S. Bergmann, M. Bauerle, M. Schmitt-Haendle, H. Walter, B. Schmidt, K. Korn, H. Sticht, et al. Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease J. Virol., March 15, 2007; 81(6): 2887 - 2898. [Abstract] [Full Text] [PDF]

				J. Kan-Mitchell, M. Bajcz, K. L. Schaubert, D. A. Price, J. M. Brenchley, T. E. Asher, D. C. Douek, H. L. Ng, O. O. Yang, C. R. Rinaldo Jr., et al. Degeneracy and Repertoire of the Human HIV-1 Gag p1777-85 CTL Response. J. Immunol., June 1, 2006; 176(11): 6690 - 6701. [Abstract] [Full Text] [PDF]

				M. J. Geels, S. A. Dubey, K. Anderson, E. Baan, M. Bakker, G. Pollakis, W. A. Paxton, J. W. Shiver, and J. Goudsmit Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation J. Virol., September 1, 2005; 79(17): 11247 - 11258. [Abstract] [Full Text] [PDF]

				B. Barugahare, C. Baker, O. K'Aluoch, R. Donovan, M. Elrefaei, M. Eggena, N. Jones, S. Mutalya, C. Kityo, P. Mugyenyi, et al. Human Immunodeficiency Virus-Specific Responses in Adult Ugandans: Patterns of Cross-Clade Recognition J. Virol., April 1, 2005; 79(7): 4132 - 4139. [Abstract] [Full Text] [PDF]