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International Immunology Advance Access originally published online on April 11, 2005
International Immunology 2005 17(5):637-648; doi:10.1093/intimm/dxh245
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Novel simian immunodeficiency virus CTL epitopes restricted by MHC class I molecule Mamu-B*01 are highly conserved for long term in DNA/MVA-vaccinated, SHIV-challenged rhesus macaques

Jin Su1, Mark A. Luscher1, Yelin Xiong1, Tarick Rustam1, Rama Rao Amara2, Eva Rakasz3, Harriet L. Robinson2 and Kelly S. MacDonald1,4

1 Department of Medicine, University of Toronto, Toronto, Canada
2 Vaccine Research Center, Yerkes Primate Research Center and Department of Microbiology and Immunology, Emory University, School of Medicine, Atlanta, GA 30322, USA
3 Wisconsin Regional Primate Research Center, Madison, WI, USA
4 Department of Microbiology, Mount Sinai Hospital, 1484-600 University Avenue, Toronto, ON M5G 1X5, Canada

Correspondence to: K. S. MacDonald; E-mail: kmacdonald{at}mtsinai.on.ca

Simian immunodeficiency virus (SIV) infection of rhesus macaques provides an excellent model for investigating the basis of protective immunity against human immunodeficiency virus (HIV). One limitation of this model, however, has been the availability of a small number of known MHC class I-restricted CTL epitopes for investigating virus-specific immune responses. We assessed CTL responses against SIV Gag in a cohort of DNA/modified vaccinia virus Ankara (MVA)-vaccinated/simian-human immunodeficiency virus (SHIV)-challenged rhesus macaques. Here, we report the identification of five novel SIV CTL epitopes in Gag for the first time (Gag39–46 NELDRFGL, Gag169–177 EVVPGFQAL, Gag198–206 AAMQIIRDI, Gag257–265 IPVGNIYRR and Gag296–305 SYVDRFYKSL) that are restricted by the common MHC class I molecule Mamu-B*01. CTL responses to these epitopes were readily detected in cryopreserved PBMC in multiple animals up to 62 weeks post-infection, both by IFN-{gamma} enzyme-linked immunospot assay and intracellular IFN-{gamma} staining. Importantly, viral sequencing results revealed that these epitopes are highly conserved in the SIV-challenged macaques over a long period of time, indicating functional constraints in these regions. Moreover, the presence of CTL responses targeting these epitopes has been confirmed in two independent cohorts of rhesus macaques that have been challenged by SHIV or SIV. Our findings provide valuable candidates for poly-epitope vaccines and for long-term quantitative monitoring of epitope-specific CD8+ responses in the context of this common Mamu class I allele. It may thus help increase the supply of rhesus macaques in which epitope-specific immunity can be studied in the context of SIV vaccine design.

Keywords: CTL, MHC, rhesus macaque, SIV, vaccine

Transmitting editor: C. Paige


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