Virus-specific T helper cells are critical for the maintenance of effective immunity in most viral infections. However, in the majority of HIV-i infected individuals, these cells are weak or absent in all stages of disease and represent a major defect in the immunological repertoire against REV-i. The exception to this observation is that individuals with long-term non-progressive HIV-1 infection as well as persons treated during acute REV-i infection are able to mount significant virus-specific T helper cell responses against several proteins produced by this virus. The purpose of this proposal is to perform a detailed characterization of the CD4+ T helper cell response to REV-i in infected persons. Specifically we propose: 1. To compare and contrast the magnitude, breadth and specificity of REV-specific T helper cell responses in persons with chronic! progressive infection, acute and early infection and long-term non-progressive infection. 2. To establish HI V-i-specific T helper cell clones and determine the precise epitopes targeted by this response, as well as the restricting HLA alleles and sequence variation within the defined epitopes. 3. To assess different methods for assessing T helper cell function, comparing and contrasting antigen-induce lymphocyte proliferation, CD4+ ELISPOT, intracellular cytokine staining, measurement of nucleotide ATP production and class II tetramer analysis. These studies will provide information critical to not only vaccine development but will also facilitate immunotherapeutic strategies to combat HIV infection.
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