AEGiS-07IAC: Promiscuity of cytotoxic T-cell epitopes from the HIV-1 envelope.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Promiscuity of cytotoxic T-cell epitopes from the HIV-1 envelope.

Int Conf AIDS 1991 Jun 16-21; 7:38 (abstract no. M.A.65)
Berzofsky JA, Shirai M; Metabolism Branch, NCI, NIH, Bethesda, MD, USA

OBJECTIVE: We observed that an immunodominant cytotoxic T lymphocyte (CTL) epitope of HIV-1 gp160, P18 (residues 315-329), is presented by class II major histocompatibility complex (MHC) molecules to helper T cells as well as by class I MHC molecules to CTL, and that several peptides of gp160 identified as helper epitopes also sensitized targets for lysis by human CD8+ CTL. We therefore asked in the mouse how broad a range of class I MHC molecules, if any, could present these peptides.

METHODS: Spleen cells from mice immunized with recombinant vaccinia expressing gp160 of HIV-1 IIIB were restimulated in culture with helper peptides T1 (428-443) or HP53 (also known as TH4.1, 834-848), or with P18, plus IL-2. Resulting effector cells were tested for lysis of autologous targets treated with the relevant peptide and transfectants or vaccinia-infected cells expressing the whole gp160 molecule.

RESULTS: P18 was presented by 5 different class I MHC molecules in the mouse. Helper peptide HP53 was also found to be presented by 4 different class I MHC molecules to CTL and T1 was presented by 2 class I MHC molecules to CTL. The CTL were CD8+ and CD4-, and killed targets expressing endogenous whole gp160 or pulsed with peptide. Overlapping and mutant peptides showed remarkable similarity in the core of the peptide required for CTL recognition of a peptide presented by distinct class I molecules, but more subtle differences in fine specificity were found.

CONCLUSIONS: The 2 helper epitopes tested were also recognized by CD8+ CTL with class I MHC molecules. One of these and the CTL epitope P18 showed a striking degree of promiscuity in the range of class I molecules that could present them. For all class I molecules, the core peptide presented was approximately the same, indicating that these are not merely adjacent or overlapping epitopes contained in the same peptide. These promiscuous epitopes should be useful in a vaccine to induce CTL immunity in an MHC diverse population. The ability to also elicit T help may give them a dual role in such a vaccine.

Keywords: AEGIS, HIV-1, Epitopes, T-Lymphocyte, T-Lymphocytes, Cytotoxic, Epitopes, T-Lymphocytes, Helper-Inducer, Peptides, Antigens, CD8, Human, Animal, Mice, ICA7
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