In this application, the Principal Investigator outlines an effort to identify """"""""protective"""""""" HIV-2 cytotoxic T-cell (CTL) epitopes that are recognized by individuals of Gambian, or sub-Saharan African, genetic backgrounds. The spread of HIV-1 into sub-Saharan countries where HIV-2 was previously endemic has resulted in the exposure of HIV-2 infected individuals to HIV-1. As some HIV2-infected individuals appear to be resistant to HIV-1 infection, some have proposed that recognition of cross-reactive CTL epitopes may contribute to protection from HIV-1. The elucidation of the roles CTL epitopes and genetic background (HLA) play in the resistance to HIV-1 infection in the presence of HIV-2 infection may contribute to our understanding of HIV immunopathogenesis. Advances in the development of computer-driven algorithms that prospectively identify putative MHC-binding regions/CTL epitopes, such as the TB/HIV research laboratory's EpiMatrix, will facilitate the comparison of immunologically relevant regions of HIV-2 sequences to HIV-1 sequences. The Investigator and her associates have demonstrated that EpiMatrix efficiently and accurately identifies MHC-binding regions from HIV protein sequences. She proposes now to apply the algorithm to the sequences of HIV-2 and HIV-1 strains that are common in West Africa, selecting putative MHC-binding regions that are conserved between these strains.
The specific aims of this project are to (1) identify conserved HIV-2/HIV-1 CTL epitopes and (2) test whether these putative epitopes are recognized by HIV-2 infected individuals. The long-term goal is to evaluate the relation between the recognition of the CTL epitopes and presence of HIV-2/HIV-1 co-infection. Modeling and MHC-binding studies will be performed in Providence, Rhode Island (United States) with the participation of MRC personnel. Selected peptides will then be tested in CTL assays using CTL lines and clones derived from HIV-2 infected individuals. The CTL assays will be performed at the Medical Research Council Laboratories in Fajara, The Gambia, West Africa, as a collaboration between TB/HIV Research lab personnel and MRC Laboratories personnel.
