Identification of Cryptic MHC I-restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

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Abstract

Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I-restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti-HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses.

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Cardinaud, S., Moris, A., Février, M., Rohrlich, P. S., Weiss, L., Langlade-Demoyen, P., … Habel, A. (2004). Identification of Cryptic MHC I-restricted Epitopes Encoded by HIV-1 Alternative Reading Frames. Journal of Experimental Medicine, 199(8), 1053–1063. https://doi.org/10.1084/jem.20031869

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