CD8+ lymphocytes from SIV-infected rhesus macaques recognize 27 different epitopes bound by the MHC class I molecule mamu-A*01: implications for vaccine design and testing.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA225)
Mothe B, Dzuris J, Vogel T, Liebl M, O'Connor D, Wang X, Wussow M, Thomson J, Altman J, Watkins D, Sette A, Allen T, Sydney J, Jing P B. Mothe, University of Wisconsin Primate Center, 1220 Capital Court, Madison, WI 53715, United States, Tel.: +1 608 265 33 79, Fax: +1 608 262 54 94, E-mail: brmothe@primate.wisc.edu
Given the important role that CD8+ lymphocytes play in controlling viral replication, it is becoming increasingly clear that an HIV vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene is a potential means to achieve these goals. To test these concepts in a relevant disease model we sought to identify multiple SIV-derived CD8+ epitopes bound by a single non-human primate MHC Class I molecule. We had previously identified the peptide binding motif of Mamu-A*01, a common rhesus macaque MHC Class I molecule that presents the immunodominant simian immunodeficiency virus (SIV) gag-derived CTL epitope p11C, C-> M (CTPYDINQM). We scanned SIV proteins for the presence of Mamu-A*01 motifs. Thirty seven peptides bound with apparent Kd values of 500 nM or lower, with 21 peptides binding better than the p11C, C-> M peptide. PBMC from SIV-infected, Mamu-A*01 macaques recognized 27 of these peptides in ELISPOT, CTL and tetramer analysis. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step towards the design of a multi-epitope vaccine for SIV and HIV.
Keywords: AEGIS, SIV, Macaca mulatta, CD8-Positive T-Lymphocytes, Epitopes, AIDS Vaccines, Peptides, HIV, Animal, Human, immunology 000709
MoOrA225
