Differential HIV epitope processing in monocytes and CD4 T cells affects cytotoxic T lymphocyte recognition

E Lazaro, SB Godfrey, P Stamegna… - The Journal of …, 2009 - academic.oup.com
E Lazaro, SB Godfrey, P Stamegna, T Ogbechie, C Kerrigan, M Zhang, BD Walker, S Le Gall
The Journal of infectious diseases, 2009academic.oup.com
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 …
Abstract
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
Oxford University Press