Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames.
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.
Cardinaud
Sylvain
S
Unité Cellulaire Antivirale, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
Moris
Arnaud
A
Février
Michèle
M
Rohrlich
Pierre-Simon
PS
Weiss
Laurence
L
Langlade-Demoyen
Pierre
P
Lemonnier
François A
FA
Schwartz
Olivier
O
Habel
André
A
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D015488:HIV Antigens / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D016364:Reading Frames; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004279:DNA, Viral; D000939:Epitopes; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I