RECOGNITION OF 2 OVERLAPPING CTL EPITOPES IN HIV-1 P17 BY CTL FROM A LONG-TERM NONPROGRESSING HIV-1-INFECTED INDIVIDUAL

HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationshi p between targeted epitopes and in vivo viral quasispecies. In this st udy, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/mu l. The dominant in vivo activat ed CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-m er SLYNTVATL (amino acids 77-85) was recognized in conjunction with HL A-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was r ecognized by HLA-All-restricted CTL, Analysis of in vivo virus sequenc es both in PBMC and plasma revealed the existence of sequence variatio n in this region, which did not affect viral replication in vitro, but decreased recognition by the All-restricted CTL response, with mainte nance of the A2-restricted response. These results indicate that an es sential region of the p17 protein can be simultaneously targeted by CT L through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In additio n, they demonstrate that Ag processing can allow for presentation of o verlapping epitopes in the same infected cell, which can be affected q uite differently by sequence variation.