COMBINED STRUCTURAL AND IMMUNOLOGICAL REFINEMENT OF HIV-1 HLA-B8-RESTRICTED CYTOTOXIC T-LYMPHOCYTE EPITOPES

This study demonstrates that use of structural information improves th e definition and optimization of cytotoxic T lymphocyte (CTL) epitopes . Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrat ed that known epitopes varied considerably at anchor positions. We use d structural information based on determination of the crystal structu re of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structu ral and immunological data more accurately defines the true peptide-bi nding motif of a restriction element than eluted peptide data allows.