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¹ Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711
² Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706
³ Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
⁴ Department of Biological Sciences, University of South Carolina, Columbia, SC 29208
⁵ The La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

CORRESPONDENCE David I. Watkins: watkins{at}primate.wisc.edu

Cryptic major histocompatibility complex class I epitopes have been detected in several pathogens, but their importance in the immune response to AIDS viruses remains unknown. Here, we show that Mamu-B*17⁺ simian immunodeficiency virus (SIV)mac239-infected rhesus macaques that spontaneously controlled viral replication consistently made strong CD8⁺ T lymphocyte (CD8-TL) responses against a cryptic epitope, RHLAFKCLW (cRW9). Importantly, cRW9-specific CD8-TL selected for viral variation in vivo and effectively suppressed SIV replication in vitro, suggesting that they might play a key role in the SIV-specific response. The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus–specific cellular immune response is likely far more complex than is generally assumed.

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