MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES

这个子项目是众多研究子项目之一

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. 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 preliminary 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. Currently, a detailed peptide binding motif is being defined. Nine novel SIV derived peptide epitopes restricted by Mamu-B*08 have been identified, while three other regions are currently being mapped to minimal optimal epitopes. 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 (and some progressors) of a highly pathogenic SIVmac239 infection. MHC class I tetramers have been successfully produced and verified for 9 minimal optimal Mamu-B*08 epitopes (eight of which have been published). Three other MHC class I tetramers are 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 SIVmac239 infection. While the overall frequency of this allele in a cohort of 196 WNPRC macaques infected with SIVmac239 is 5.6% (11 of 196), the frequency of this allele among elite controllers is 37.5% (6 of 16). Furthermore, the binding motif of the Mamu-B*08 allele is similar to that of HLA-B*27, an allele in humans associated with control of HIV. Additional testing is currently ongoing to investigate how close the peptide binding motif is between these two alleles. This research used WNPRC Immunogenetics & Virology Services and Animal Services.