CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects
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CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects William R Rodriguez†1,2, Marylyn M Addo†1,2, Almas Rathod1, Cecily A Fitzpatrick1, Xu G Yu1, Beth Perkins1, Eric S Rosenberg1, Marcus Altfeld1,2 and Bruce D Walker*1,2,3 Address: 1Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, USA, 2Harvard Division of AIDS, Harvard Medical School, Boston, MA, USA and 3Howard Hughes Medical Institute, Charlestown, MA, USA Email: William R Rodriguez - [email protected]; Marylyn M Addo - [email protected]; Almas Rathod - [email protected]; Cecily A Fitzpatrick - [email protected]; Xu G Yu - [email protected]; Beth Perkins - [email protected]; Eric S Rosenberg - [email protected]; Marcus Altfeld - [email protected]; Bruce D Walker* - [email protected] * Corresponding author †Equal contributors
Published: 21 May 2004 Journal of Translational Medicine 2004, 2:15
Received: 26 February 2004 Accepted: 21 May 2004
This article is available from: http://www.translational-medicine.com/content/2/1/15 © 2004 Rodriguez et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract Background: CD8+ T cell responses are known to be important to the control of HIV-1 infection. While responses to reverse transcriptase and most structural and accessory proteins have been extensively studied, CD8 T cell responses specifically directed to the HIV-1 enzymes Protease and Integrase have not been well characterized, and few epitopes have been described in detail. Methods: We assessed comprehensively the CD8 T cell responses to synthetic peptides spanning Protease and Integrase in 56 HIV-1 infected subjects with acute, chronic, or controlled infection using IFN-γ-Elispot assays and intracellular cytokine staining. Fine-characterization of novel CTL epitopes was performed on peptide-specific CTL lines in Elispot and 51Chromium-release assays. Results: Thirteen (23%) and 38 (68%) of the 56 subjects had detectable responses to Protease and Integrase, respectively, and together these targeted most regions within both proteins. Sequence variability analysis confirmed that responses cluster largely around conserved regions of Integrase, but responses against a large, highly conserved region of the N-terminal DNA-binding domain of Integrase were not readily detected. CD8 T cell responses targeted regions of Protease that contain known Protease inhibitor mutation residues, but strong Protease-specific CD8 T cell responses were rare. Fine-mapping of targeted epitopes allowed the identification of three novel, HLA class I-restricted, frequently-targeted optimal epitopes. There were no significant correlations between CD8 T cell responses to Protease and Integrase and clinical disease category in the study subjects, n
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