Efficient processing of the immunodominant, HLA-A*0201-restricted human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitope despite multiplevariations in the epitope flanking sequences

Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immuno genic peptide. However, the frequency of such an escape mechanism has not b een determined. To investigate whether naturally occurring variations in th e flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag s equences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants w ere efficiently processed from minigene expressing vectors and from sis HIV -1 Gag variants expressed by recombinant vaccinia virus constructs. Further more, SL9-specific CTL clones derived from multiple donors efficiently inhi bited virus replication when added to HLA-*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immun odominant CTL response is not frequently accomplished by changes in the epi tope flanking sequences.