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

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dc.contributor.author Rathod, Almas
dc.contributor.author Fitzpatrick, Cecily A
dc.contributor.author Perkins, Beth
dc.contributor.author Rodriguez, William Richard
dc.contributor.author Addo, Marylyn Martina
dc.contributor.author Yu, Xu
dc.contributor.author Rosenberg, Eric Scott
dc.contributor.author Altfeld, Marcus
dc.contributor.author Walker, Bruce David
dc.date.accessioned 2011-05-10T01:45:09Z
dc.date.issued 2004
dc.identifier.citation Rodriguez, William R., Marylyn M. Addo, Almas Rathod, Cecily A. Fitzpatrick, Xu G. Yu, Beth Perkins, Eric S. Rosenberg, Marcus Altfeld, and Bruce D. Walker. 2004. CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects. Journal of Translational Medicine 2: 15. en_US
dc.identifier.issn 1479-5876 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4885971
dc.description.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 \(^{51}\)Chromium-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, nor was there a correlation with viral load. Conclusions: These findings confirm that CD8 T cell responses directed against HIV-1 include potentially important functional regions of Protease and Integrase, and that pharmacologic targeting of these enzymes will place them under both drug and immune selection pressure. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1479-5876-2-15 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC441415/pdf/ en_US
dash.license LAA
dc.title CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Journal of Translational Medicine en_US
dash.depositing.author Rodriguez, William Richard
dc.date.available 2011-05-10T01:45:09Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases en_US

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