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EXTENSIVE HLA CLASS I BINDING PROMISCUITY AMONG EBV- AND HIV- DERIVED CYTOTOXIC T LYMPHOCYTE EPITOPES.
Nicole Frahm, PhD, Karina Yusim, PhD, Peter Hraber, PhD, Sharon Adams, PhD, Franco Marincola, MD, PhD, Bette Korber, PhD and Christian Brander, PhD. Charlestown MA, USA, Massachusetts General Hospital, 02129, Partners AIDS Research Center; Los Alamos NM, USA, Los Alamos National Laboratory, 87545, Theoretical Biology and Biophysics; Santa Fe NM, USA, 87545, Santa Fe Institute and Bethesda MD, USA, NIH, Clinical Center.

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In the past, more than 200 HIV and 90 EBV derived CTL epitopes have been identified and well characterized in terms of their minimal length and their HLA restriction. Combinations of these antigens in epitope-based vaccines is being employed to achieve wide population coverage, however, HLA diversity in different ethnicities could limit the usefulness of this approach. We have tested a total of 275 viral epitopes in in vitro CTL assays, in which PBMC from HIV- and EBV-infected individuals are incubated with antigen and T cell activation is assessed based on the expression of IFN-g. Of more than 2300 responses detected, 38% were found in individuals expressing the originally reported restricting HLA allele. An additional 22% of the responses were detected in individuals not expressing the original allele but an allele that fell into the same HLA supertype as the original allele. This left 40% of responses for which presentation on an alternative HLA class I molecule can be postulated, indicating promiscuous epitope binding to HLA class I alleles outside of the described HLA supertypes. When analyzed on a single peptide level, 230 of the 275 epitopes were recognized at least once on alternative class I allele(s). These data demonstrate an unprecedented degree of HLA binding promiscuity among viral CTL epitopes and suggest that HLA cross-presentation patterns may be better represented as a network rather than supertypes.