This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.To work on developing a vaccine for HIV, we will identify additional epitopes for cytotoxic and helper T cells and use this information to develop unique reagents for following immune responses.The binding motif of Mamu-B*08 has been determined and shown to contain a dominant preference for arginine at the P2 anchor position along with a dominant preference for leucine at the P9 C-terminus. Nine novel SIV derived peptide epitopes restricted by Mamu-B*08 have been identified. These have been mapped by a combination of intracellular cytokine staining and ELISPOT in responder cell lines or PBMC's derived from animals that are elite controllers of a highly pathogenic SIVmac239 infection. Tetramers have been successfully produced and verified for 5 of the 9 epitopes thus far, with the other 4 under development. It is important to note that MHC typing data shows that Mamu-B*08 is over represented among a cohort of rhesus macaques that control SIV infection. While the overall frequency of this allele in a cohort of 120 WNPRC macaques infected with SIV is 5% (6 of 120), the frequency of this allele among elite controllers is 40% (4 of 10). Furthermore, the binding motif of this allele is similar to that of HLA-B*27 , an allele in humans associated with control of HIV. Four CD4+ T cell epitopes and their restricting alleles have been defined for 4 SIV derived peptides using MHC class II transferents. These responses have been defined in rhesus macaques that control their SIV viral loads, but no causal relationship has been established. This research used WNPRC Immunogenetics & Virology Services and Animal Services.
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