THE ORGANIZATION OF HUMAN-LEUKOCYTE ANTIGEN CLASS-I EPITOPES IN HIV GENOME PRODUCTS - IMPLICATIONS FOR HIV EVOLUTION AND VACCINE DESIGN

Knowledge of human leucocyte antigen (HLA) peptide binding motifs perm its 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) o f different genetic lineages provides a map of the genetic organizatio n 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 sp ectrum: local organization is characterized by anomalously long runs b etween motifs. The former is expected simply due to the fact that moti fs often have overlapping anchor residue sets. A detailed statistical analysis of the latter, however, shows that the length of the runs can not be accounted for by chance alone. Although motif clusters show no preference to be in either conserved or variable regions, low motif de nsity stretches occur preferentially in variable portions of the prote in sequence, which suggests that the virus may be mutating to evade th e cellular arm of the immune system. (C) 1997 Elsevier Science Ltd.