MAPPING OF IMMUNODOMINANT CD8+ AND CD4+ T LYMPHOCYTE EPITOPES IN RHESUS CMV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In order to conduct a comprehensive evaluation of CMV-specific cellular immunity in rhesus macaques, immunodominant CD8+ and CD4+ T lymphocyte epitopes in rhesus CMV are being mapped using a variety of techniques including interferon-gamma ELISPOT assays, intracellular cytokine staining assay and tetramers. Four Mamu-A*01 restricted epitopes have been identified and their tetramers synthesized. In addition vaccinia recombinants expressing the rhesus CMV immediate early 1 and 2 proteins, pp65 protein and IL-10 protein have been constructed, and 15 aa overlapping 11 peptides spanning these rhesus CMV proteins have been synthesized. Results to date show that naturally CMV-infected breeder rhesus macaques have high frequencies of circulating CD8+ T lymphocytes (as high as 6 percent) targeting epitopes in the rhesus CMV immediate early proteins. Mapping of immunodominant epitopes using overlapping peptides has revealed several new CMV epitopes in the immediate early and pp65 genes. The MHC Class I restriction of these epitopes is being determined. These studies will enable more precise assessment of the protective correlates of CMV-specific cellular immunity and help in the design of appropriate vaccine strategies for prevention of CMV disease.