IDENTIFICATION OF HIV PROTEIN-DERIVED CYTOTOXIC T-LYMPHOCYTE (CTL) EPITOPES FOR THEIR POSSIBLE USE AS SYNTHETIC VACCINE

CTL are by far the most important defence mechanisms against viral inf ections, and many attempts have been undertaken to induce protective C TL in vivo. In order to identify CTL epitopes for their possible use a s peptide-vaccine candidates, HIV proteins were screened for peptide s equences which (i) fulfil the binding motif of the HLA-A2.1 molecule, and (ii) are involved in the natural immune response to HIV. From 73 n onameric peptides satisfying the binding motif, 20 peptides were synth esized and their binding to HLA-A2.1 was monitored by measuring the ex pression of HLA-A2.1 molecules on the cell surface of the mutant cell line T2. To evaluate the involvement in natural HIV infection, strongl y binding peptides were used in cytotoxicity assays to assess their ca pacity to generate a peptide-specific CTL response in vitro. From 20 n onameric peptides synthesized, only five showed strong binding to HLA- A2.1. All five binding peptides had the secondary anchor residues, rec ently proposed by Ruppert et al. [1] to be required for binding to HLA -A2.1. The discrimination between bound and unbound peptides confirmed the importance of these secondary anchor residues which, beside the k nown binding motif, may dictate if a peptide can bind to HLA-A2.1 or n ot. In HIV- donors, no CTL activity against any of the HIV-derived pep tides was detectable after a 12-day in vitro stimulation. In contrast, HIV-infected persons showed a cytotoxic response against peptide-labe lled target cells, suggesting that they had developed upon HIV infecti on a cytotoxic immune response against the identified CTL epitopes.