The organization of human leucocyte antigen class I epitopes in HIV genome products: implications for HIV evolution and vaccine design.

Knowledge of human leucocyte antigen (HLA) peptide binding motifs permits rapid selection of candidate viral protein fragments for induction of T cell-mediated immunity. A search for HLA class I peptide binding motifs in structural proteins of human immunodeficiency virus (HIV) of different genetic lineages provides a map of the genetic organization of potential T cell antigenic sites, and at the same time identifies all motifs in highly conserved regions of HIV-1 env, gag and pol. The density of motifs is anomalous at both the high and low end of the spectrum: local organization is characterized by clustering in relatively short regions, while large scale organization is characterized by anomalously long runs between motifs. The former is expected simply due to the fact that motifs often have overlapping anchor residue sets. A detailed statistical analysis of the latter, however, shows that the length of the runs cannot be accounted for by chance alone. Although motif clusters show no preference to be in either conserved or variable regions, low motif density stretches occur preferentially in variable portions of the protein sequence, which suggests that the virus may be mutating to evade the cellular arm of the immune system.