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Journal of Virology, October 2002, p. 10219-10225, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10219-10225.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Study of Antigen-Processing Steps Reveals Preferences Explaining Differential Biological Outcomes of Two HLA-A2-Restricted Immunodominant Epitopes from Human Immunodeficiency Virus Type 1

Institut National de la Santé et de la Recherche Médicale Unité 445,¹ Centre National de la Recherche Scientifique Unité Propre de Recherche 415, 75014 Paris,³ Centre National de la Recherche Scientifique Unité Propre de Recherche 9021, 67000 Strasbourg,² Institut National de la Santé et de la Recherche Médicale Unité 25, 75743 Paris, France⁴

Received 29 April 2002/ Accepted 16 July 2002

Cytotoxic T-lymphocyte (CTL) responses directed to different human immunodeficiency virus (HIV) epitopes vary in their protective efficacy. In particular, HIV-infected cells are much more sensitive to lysis by anti-Gag/p17(77-85)/HLA-A2 than to that by anti-polymerase/RT(476-484)/HLA-A2 CTL, because of a higher density of p17(77-85) complexes. This report describes multiple processing steps favoring the generation of p17(77-85) complexes: (i) the exact COOH-terminal cleavage of epitopes by cellular proteases occurred faster and more frequently for p17(77-85) than for RT(476-484), and (ii) the binding efficiency of the transporter associated with antigen processing was greater for p17(77-85) precursors than for the RT(476-484) epitope. Surprisingly, these peptides, which differed markedly in their antigenicity, displayed qualitatively and quantitatively similar immunogenicity, suggesting differences in the mechanisms governing these phenomena. Here, we discuss the mechanisms responsible for such differences.

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