Recognition of a Small Number of Diverse Epitopes Dominates the Cytotoxic T Lymphocyte Response to HIV Type 1 in an Infected Individual

Abstract

Mitogen-activated T cell lines may be reproducibly used to identify relatively conserved HIV-1 epitopes that dominate CTL recognition of HIV-infected cells. Using a combination of nested truncations of HIV-vaccinia recombinants encoding HIV-1_LAI Env and overlapping peptides that span the coding regions of the HIV-1 SF2 subclone of env, gag, nef, rev, and tat, we have mapped the immunodominant, relatively conserved CTL epitopes recognized by 25 HIV-seropositive individuals with CD4 counts between 100 and 500/mm³ and no history of AIDS opportunistic infection. We could characterize at least 1 peptide CTL epitope recognized by the T cell lines of 18 of 25 of the subjects; the T cell lines from 2 additional subjects recognized HIV-vaccinia presenting targets, but no dominant peptide epitope was identified. CTL epitopes were most frequently encoded by gag (recognized by 16 of 25 patient T cell lines), followed by nef and env (11 of 25 each), and the RT region of pol (9 of 25). Tat and Rev were rarely the sites of CTL epitopes. The identified epitopes occurred predominantly in relatively conserved regions of HIV-1. The mean number of HIV peptides identified at a single time for each cell line was 2.7 ± 1.7. Although no single peptide dominated CTL recognition in more than four individuals, clusters of epitopes were found in the N-terminal region of gp160 and in two central regions of Nef. The dominant HIV-1 CTL epitopes in infected patients were not predictable on the basis of MHC expression and varied widely in an MHC-diverse population.