OVERLAPPING EPITOPES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 PRESENTED BY HLA-A, HLA-B, AND HLA-C MOLECULES - EFFECTS OF VIRAL VARIATION ON CYTOTOXIC T-LYMPHOCYTE RECOGNITION

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (C TL) are thought to exert immunologic selection pressure in infected pe rsons, yet few data regarding the effects of this constraint on viral sequence variation in vivo, particularly in the highly variable Env pr otein, are available, In this study, CD8(+) HIV type 1 (HIV-1) envelop e-specific CTL clones specific for gp120 were isolated from peripheral blood mononuclear cells of four HIV-infected individuals, all of whic h recognized the same 25-amino-acid (aa) peptide (aa 371 to 395), whic h is partially contained in the CD4-binding domain of HIV-1 gp120. Fin e mapping studies revealed that two of the clones optimally recognized the 9-aa sequence 375 to 383 (SFNCGGEFF), while the two other clones optimally recognized the epitope contained in the overlapping 9-aa seq uence 376 to 384 (FNCGGEFFY). Lysis of target cells by the two clones recognizing aa 375 to 383 was restricted by HLA B15 and Cw4, respectiv ely, whereas both clones recognizing aa 376 to 383 were restricted by HLA A29. Sequence variation, relative to the IIIB strain sequence used to identify CTL clones, was observed in autologous viruses in the epi tope-containing region in all four subjects, However, poorly recognize d autologous sequence variants were predominantly seen for the A29-res tricted clones, whereas the clones specific for SFNCGGEFF continued to recognize the predominant autologous sequences, These results suggest that the HLA profile of an individual may not only be important in de termining the specificity of CTL recognition but may also affect the a bility to recognize virus variants and suppress escape from CTL recogn ition. These results also identify overlapping viral CTL epitopes whic h can be presented by HLA A, B, and C molecules.