Early antigen presentation of protective HIV-1 KF11Gag and KK10Gag epitopes from incoming viral particles facilitates rapid recognition of infected cells by specific CD8+ T cells

Early antigen presentation of protective HIV-1 KF11Gag and KK10Gag epitopes from incoming viral particles facilitates rapid recognition of infected cells by specific CD8+ T cells

Data de publicació online: 19/12/2012 Revista: Journal of Virology

Abstract:

CD8+ T cells are major players in antiviral immunity against HIV-1 through recognition of viral epitopes presented on the surface of infected cells. However, the early events involving HIV-1 epitope presentation to CD8+ T cells remain poorly understood but nonetheless crucial for the rapid clearance of virus infected cells. Here, we comprehensively studied the kinetics of antigen presentation of two protective epitopes, KF11(Gag) and KK10(Gag), restricted by HLA alleles B*57:01 and B*27:05, respectively, and compared these to KY9(Pol) and VL9(Vpr) epitopes in a single cycle of HIV-1 replication. We consistently demonstrate differences in epitope presentation kinetics with very early presentation, within 3 hours post-infection, for the protective KF11(Gag,) KK10(Gag) epitopes and KY9(Pol), but only late presentation for VL9(Vpr). We show that this early presentation relies on the antigen being presented from incoming viral particles and is correlated with rapid CD8+ T cell activation and clearance of virus infected cells. Additionally, our data indicate a dose response dependency between the levels of CD8+ T cell activation and the amount of virus inoculum. These data reflect a proof of principle emphasizing the importance of identifying early-presented viral epitopes for rapid elimination of HIV-1 infected cells.

 

Read abstract online in Journal of Virology: http://jvi.asm.org/content/early/2012/12/12/JVI.02131-12.abstract

Autors: Kløverpris HN, Payne RP, Sacha JB, Rasaiyaah JT, Chen F, Takiguchi M, Yang OO, Towers GJ, Goulder P, Prado JG.   1Department of Paediatrics, University of Oxford, Peter Medawar Building, OX1 3SY, United Kingdom 2Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, Oregon Health & Science University, USA 3Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom 4Department of Sexual Health, Royal Berkshire Hospital, Reading RG1 5AN, United Kingdom 5Centre for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan 6Departments of Medicine and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA 7AIDS Research Institute IrsiCaixa, Hospital Germans Trias i Pujol, 08916 Badalona, Spain  

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