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Identification of Multiple Simian Immunodeficiency Virus (SIV)-Specific CTL Epitopes in Sooty Mangabeys with Natural and Experimentally Acquired SIV Infection¹

Amitinder Kaur^2,*, Janet Yang^*, Donna Hempel^*, Linda Gritz, Gail P. Mazzara, Harold McClure and R. Paul Johnson^*,

^* Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772; Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, MA 02129; Therion Biologics Corp., Cambridge, MA 02142; and Divisions of Research Resources and Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322

Host immune responses to SIV infection in sooty mangabeys are likely to be an important determinant of how such nonhuman primate species maintain asymptomatic lentivirus infection. We have previously described two patterns of asymptomatic SIV infection in sooty mangabeys: low viral loads with vigorous SIV-specific CTL activity in SIVmac239-infected sooty mangabeys, and high viral loads with generally weak or absent SIV-specific CTL activity in naturally infected sooty mangabeys. To define the specificity of the CTL response in SIV-infected mangabeys, we characterized CTL epitopes in two naturally infected and three SIVmac239-infected sooty mangabeys. Compared with that in SIVmac239-infected mangabeys, the yield of SIV-specific CTL clones was significantly lower in naturally infected sooty mangabeys. All CTL clones were phenotypically CD3⁺ CD8⁺, and lysis was MHC restricted. Seven SIV CTL epitopes were identified in five sooty mangabeys: one in Gag and three each in Nef and Envelope (Env). The CTL epitopes mapped to conserved regions in the SIV genome and were immunodominant. Several similar or identical CTL epitopes were recognized by both naturally infected and SIVmac239-infected mangabeys that shared class I MHC alleles. To our knowledge, this is the first report of SIV-specific CTL epitopes in sooty mangabeys. Longitudinal studies of viral load and sequence variation in CTL epitopes may provide useful information on the role of CTL in control or persistence of SIV infection in sooty mangabeys.

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