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Recognition of Two Overlapping CTL Epitopes in HIV-1 p17 by CTL from a Long-Term Nonprogressing HIV-1-Infected Individual¹

Thomas Harrer^2,*,, Ellen Harrer^*,, Peter Barbosa^3,, Friedemann Kaufmann^¶, Ralf Wagner^¶, Susanne Brüggemann^*, Joachim R. Kalden^*, Mark Feinberg^,§, R. Paul Johnson, Susan Buchbinder^|| and Bruce D. Walker

^* Department of Medicine III with Institute of Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany; Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129; Gladstone Institute, San Francisco, CA 94141; ^§ Center of AIDS Research, San Francisco, CA 94141; ^¶ Institute of Medical Microbiology, University of Regensburg, Regensburg, Germany; and ^|| AIDS Office, Department of Public Health, San Francisco, CA 94140

HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/µl. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77–85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83–91) was recognized by HLA-A11-restricted CTL. Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the A11-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation.

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