AEGiS-14IAC: Whole genome analysis of HIV-1 specific cytotoxic T lymphocyte (CTL) responses on single epitope level in different groups of HIV-1 infected individuals.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Whole genome analysis of HIV-1 specific cytotoxic T lymphocyte (CTL) responses on single epitope level in different groups of HIV-1 infected individuals.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1182)

Addo MM, Yu XG, Rathod A, Cohen D, Eldridge R, Johnston MN, Blackard JT, Brander C, Boswell S, Goulder PJ, Rosenberg ES, Altfeld M, Walker BD
Partners AIDS Research Center/MGH, Boston, United States

BACKGROUND: Cellular immune responses play a critical role in the control of HIV-1. However, no comprehensive analysis of HIV-1 specific T lymphocyte responses directed against the whole expressed genome on the single epitope level has been performed thus far.

METHODS: PBMC from 40 HIV-1 infected individuals (10 treated during primary infection, 10 with chronic treated infection and 20 individuals with untreated chronic infection representing a wide range of viral loads) were screened for HIV-specific CD 8T cell responses by Elispot using a peptide-matrix system we recently described. The peptide matrix consisted of 104 peptide pools representing 505 overlapping peptides spanning all expressed HIV-1 proteins (Gag= p17, p24, p15; Pol= Integrase, Protease, RT; Vif; Vpr; Vpu; Env= gp41, gp120; Tat, Rev, Nef). Total breadth and magnitude of T cell responses in each individual were assessed on the single epitope level.

RESULTS: All expressed HIV genes were targets of HIV-1 specific CTL in this study cohort. Gag was the most frequently targeted protein followed by Nef and Pol. The number of total recognized HIV-1 epitopes per subject ranged from 2 to 40 (median: 16). The magnitude of responses demonstrated a wide range, but in most cases responses directed against Gag contributed most importantly to the magnitude of the total HIV-1 specific T cell response. P24-Gag, Nef and p17-Gag were the proteins with the highest epitope density at 1.6, 1.17 and 1.16 epitopes per 100 amino acids, respectively.

CONCLUSIONS: Using a peptide matrix system allows for the rapid screening of lymphocyte responses directed against the whole expressed HIV-1 genome with high sensitivity and specificity. This study also demonstrates that all HIV-1 proteins can serve as targets for CTL. HIV-1-specific immune responses show a wide spectrum in breadth and magnitude of responses in different patient cohorts and are directed against a large number of different epitopes and proteins.

Keywords: AEGIS, HIV-1, T-Lymphocytes, Cytotoxic, Epitopes, HIV Infections, Viral Load, Single Person, T-Lymphocytes, HIV Seropositivity, HIV-1 Reverse Transcriptase, Human, immunology

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