Differential HIV epitope processing in monocytes and CD4 T cells affects cytotoxic T lymphocyte recognition.
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.
Lazaro
Estibaliz
E
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Boston, MA, USA.
Godfrey
Sasha Blue
SB
Stamegna
Pamela
P
Ogbechie
Tobi
T
Kerrigan
Christopher
C
Zhang
Mei
M
Walker
Bruce D
BD
Le Gall
Sylvie
S
D017951:Antigen Presentation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D000939:Epitopes / Q000502:physiology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000939:Epitopes