CD8 + T Cell Recognition of Cryptic Epitopes Is a Ubiquitous Feature of AIDS Virus Infection

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Abstract
Vaccines designed to elicit AIDS virus-specific CD8 + T cells should engender broad responses. Emerging data indicate that alternate reading frames (ARFs) of both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode CD8 + T cell epitopes, termed cryptic epitopes. Here, we show that SIV-specific CD8 + T cells from SIV-infected rhesus macaques target 14 epitopes in eight ARFs during SIV infection. Animals recognized up to five epitopes, totaling nearly one-quarter of the anti-SIV responses. The epitopes were targeted by high-frequency responses as early as 2 weeks postinfection and in the chronic phase. Hence, previously overlooked ARF-encoded epitopes could be important components of AIDS vaccines.