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Differential HIV Epitope Processing in Monocytes and CD4 T Cells Affects Cytotoxic T Lymphocyte Recognition

  作者 Lazaro, E; Godfrey, SB; Stamegna, P; Ogbechie, T; Kerrigan, C; Zhang, M; Walker, BD; Le Gall, S  
  选自 期刊  Journal of Infectious Diseases;  卷期  2009年200-2;  页码  236-243  
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[摘要]The ability of cytotoxic T lymphocytes (CTLs) to clear virus-infected cells is dependent on the presentation of viral peptides processed intracellularly and displayed by major histocompatibility complex class I. Most CTL functional assays use exogenously added peptides, a practice that does not account for the kinetics and quantity of antigenic peptides produced by infectable cells. Here, we examined the relative ability of 2 major human immunodeficiency virus-infectable cell subsets-CD4 T lymphocytes and monocytes-to produce antigenic peptides, using cytosol as a source of peptidases and mass spectrometry to define the degradation products. We show clear subset-specific differences in the kinetics of peptide production and the ability of the peptides produced to sensitize cells for lysis by CTLs, with primary CD4 T lymphocytes having significantly lower proteolytic activity than monocytes. These differences in epitope processing by cell subsets may affect the efficiency of CTL-mediated clearance of infected subsets and contribute to the establishment of chronic infection.

 
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