Effective lysis of HIV-1-infected primary CD4+ T cells by a cytotoxic T-lymphocyte clone directed against a novel A2-restricted reverse-transcriptase epitope.
Most HIV-specific cytotoxic T-lymphocyte (CTL) epitopes have been identified using peptide-pulsed and recombinant vaccinia virus-infected targets. These systems may not accurately reflect the ability of epitopes to be presented by HIV-infected T cells. Recent studies suggest, in fact, that some CTL epitopes are poorly presented on HIV-infected cells. In this study, we have identified a novel A2.1-restricted HIV reverse-transcriptase (RT) epitope and investigated the presentation of this epitope by HIV-infected primary CD4+ T cells and T-cell lines. A CD8+ CTL clone, isolated from a seropositive subject that recognized a novel A2-restricted epitope KYTAFTIPSI (aa 293-302) in RT, was used for these studies. Primary CD4+ T cells and the CD4+ T-cell line T1 were infected with virus from T1-nPLAP, a cell line stably transfected with HXB-nPLAP, a molecular construct of HIV linked to a placental alkaline phosphatase (PLAP) marker gene. A uniformly infected cell population, obtained by immunomagnetic selection for PLAP expression, was used as targets in CTL assays. HIV-infected T cells were lysed by CTL recognizing this RT epitope as effectively as peptide-pulsed targets. This suggests that some RT epitopes are good targets for CTL recognition.
The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
P
P
Shankar
H
H
Sprang
J
J
Lieberman
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D008863:Microspheres; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000939:Epitopes; D054303:HIV Reverse Transcriptase