| | |  | | | | Record from Web of Science® | | | | | | |
| IDENTIFICATION OF OVERLAPPING HLA CLASS I-RESTRICTED CYTOTOXIC T-CELL EPITOPES IN A CONSERVED REGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN - DEFINITION OF MINIMUM EPITOPES AND ANALYSIS OF THE EFFECTS OF SEQUENCE VARIATION |
|
|
| Author(s): JOHNSON RP, TROCHA A, BUCHANAN TM, WALKER BD |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 175 Issue: 4 Pages: 961-971 Published: APR 1 1992 |
| Times Cited: 128 References: 64 |
| Abstract: Although the immunologic basis of protective immunity in human immunodeficiency virus type 1 (HIV-1) infection has not yet been defined, virus-specific cytotoxic T lymphocytes (CTL) are likely to be an important host defense and may be a critical feature of an effective vaccine. These observations, along with the inclusion of the HIV-1 envelope in the majority of vaccine candidates presently in clinical trials, underscore the importance of the precise characterization of the cellular immune responses to this protein. Although humoral immune responses to the envelope protein have been extensively characterized, relatively little information is available regarding the envelope epitopes recognized by virus-specific CTL and the effects of sequence variation within these epitopes. Here we report the identification of two overlapping CTL epitopes in a highly conserved region of the HIV-1 transmembrane envelope protein, gp41, using CTL clones derived from two seropositive subjects. An eight-amino acid peptide was defined as the minimum epitope recognized by HLA-B8-restricted CTL derived from one subject, and in a second subject, an overlapping nine-amino acid peptide was identified as the minimal epitope for HLA-B14-restricted CTL clones. Selected single amino acid substitutions representing those found in naturally occurring HIV-1 isolates resulted in partial to complete loss of recognition of these epitopes. These data indicate the presence of a highly conserved region in the HIV-1 envelope glycoprotein that is immunogenic for CTL responses. In addition, they suggest that natural sequence variation may lead to escape from immune detection by HIV-1-specific CTL. Since the region containing these epitopes has been previously shown to contain an immunodominant B cell epitope and also overlaps with a major histocompatibility complex class II T cell epitope recognized by CD4+ CTL from HIV-1 rgp160 vaccine recipients, it may be particularly important for HIV-1 vaccine development. Finally, the identification of minimal CTL epitopes presented by class I HLA molecules should facilitate the definition of allele-specific motifs. |
| Document Type: Article |
| Language: English |
Addresses:
1. MASSACHUSETTS GEN HOSP, INFECT DIS UNIT, GRAY 5, BOSTON, MA 02114 USA
2. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA
3. UNIV WASHINGTON, SEATTLE, WA 98144 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: HL014 |
| ISSN: 0022-1007 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |