T cell multideterminant regions in the human immunodeficiency virus envelope: toward overcoming the problem of major histocompatibility complex restriction

Abstract

Helper T cell determinants should be an Important component of an anti-human Immunodeflciency virus (HIV) vaccine aimed at either antibody or cytotoxic T cell Immunity. However, model protein studies have raised concern about the usefulness of any single determinant, because a given determinant is likely to be seen by only a small subset of major histocompatiblllty complex (MHC) types within the population. Here, we use 44 peptldes, Including ones predicted and not predicted on the basis of amphipathicity to be potential T cell sites, to locate T cell antlgenic determinants recognized by mice of four MHC haplotypes immunized with the whole gpl6O envelope protein. Although the preselectlon of peptides necessitates caution in a statistical analysis, α-amphipathic peptides predominated among sites eliciting the strongest response. Although we have not tested the entire sequence, we have identified six multideterminant regions, in which overlapping peptides are recognized by mice of either three or all four MHC types. Four of the six regions have sequences relatively conserved among HIV.1 isolates. The existence of such multideterminant regions recognized by multiple MHC haplotypes suggests the possibilIty that use of peptides longer than a minimal determinant and containing several overlapping determinants may be a possible approach to circumvent the serious problem of MHC restriction in peptide vaccines aimed at eliciting T cell immunity.