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.
CITATION STYLE
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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