An unanticipated lack of consensus cytotoxic T lymphocyte epitopes in HIV-1 databases: the contribution of prediction programs

Abstract

Background: Most consensus HIV-1-specific cytotoxic T lymphocytes epitopes presented via intensively studied HLA molecules are thought to be known Objective: To identify possible novel HIV-1 epitopes for HLA-B27 and HLA-B57; two HLA types which are abundantly studied because of their correlation with slow HIV disease progression. Methods: HIV-1 consensus subtype B sequences were analysed using peptide prediction programs based on major histocompatibility complex binding, proteasomal cleavage and TAP (transporter associated with antigen processing) transport. Recognition of the novel identified epitopes by cytotoxic T lymphocytes was tested using interferon-[gamma] ELISpot assay. Results: In total, 22 novel epitopes predicted to be presented by either HLA-B27 or HLA-B57 were selected. Of these, 86% elicited significant immune responses in HIV-1-infected individuals. Conclusions: These data show that numerous HIV-1 epitopes remain to be identified, and that prediction programs are powerful tools for this purpose.