Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames.

Sylvain Cardinaud (1) , Arnaud Moris (2) , Michèle Février (3) , Pierre-Simon Rohrlich (1) , Laurence Weiss (4) , Pierre Langlade-Demoyen (1) , François A Lemonnier (1) , Olivier Schwartz (2) , André Habel (1)

1 Immunité Cellulaire Antivirale
2 Virus et Immunité
3 Immunopathologie Virale
4 HEGP - Hôpital Européen Georges Pompidou [APHP]

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.

Domains: Life Sciences [q-bio]

Sylvain Cardinaud, Arnaud Moris, Michèle Février, Pierre-Simon Rohrlich, Laurence Weiss, et al.. Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames.. Journal of Experimental Medicine, 2004, 199 (8), pp.1053-63. ⟨10.1084/jem.20031869⟩. ⟨pasteur-01372661⟩