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33 Assessment and Comparison of HIV-1-Specific T-Cell Responses in Long-Term Nonprogressors (LTNPs) and Acute Seroconverters
L. Cosimi*, H. Truong, B. Wilkes, D. Strick, B. D. Walker, and E. S. Rosenberg
Partners AIDS Res. Ctr., Massachusetts Gen. Hosp., and Harvard Med. Sch., Boston, MA, USA
Background: There is increasing evidence that CD4+ T cells play a critical role in maintenance of virus-specific immunity in most chronic viral infections. A successful immunotherapeutic strategy is likely to require induction of HIV-1-specific antibody, CD8+ CTL, and CD4+ T-helper responses. The identification of a repertoire of dominant HIV-1-specific T-helper epitopes that can bind to the most common HLA alleles in the population will be critical to this process. We have set out to determine the breadth and specificity of HIV-1-specific T-cell responses and to compare these responses in 2 cohorts of patients: long-term nonprogressors and acute seroconverters.
Methods: Five LTNPs and 15 treated acute seroconverters were screened using a panel of overlapping peptides spanning the Gag protein. CD4+-specific T-cell responses were assessed via IFN-gamma production by ELISPOT assays and intracellular cytokine staining as well as by lymphocyte proliferation assay.
Results: Strong Gag-specific CD4+ responses were noted in all of the LTNPs. There was a range of responses throughout Gag with several novel epitopes identified. Two epitopes, p24(31-52) and p24(131-152), were recognized by 4 out of 5 subjects despite differing class II HLA types. In addition, gag-specific responses were noted in the majority of treated acute seroconverters. Although the breadth and strength of responses were less than in those controlling viremia, similar epitopes were identified and recognized in up to 30% of subjects. No CD4+ T-cell responses were seen in HIV-1-seronegative controls.
Conclusions: Individuals successfully controlling viral replication have a large breadth of Gag-specific CD4+ responses with several epitopes that are commonly recognized and able to be presented by multiple class II HLA types. These epitopes are also recognized in some individuals with treated acute HIV-1. Further characterization of these epitopes may be useful for the development of vaccine strategies and other immunotherapeutic interventions.
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