Direct visualization of the dynamics of antigen presentation in human cells infected with cytomegalovirus revealed by antibodies mimicking TCR specificity

Oryan Makler, Kfir Oved, Nir Netzer, Dana Wolf, Yoram Reiter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

There are no direct means to study class I MHC presentation in human normal or diseased cells. Using CMV-infected human cells and applying novel mAb that mimic T-cell receptor specificity directed toward the immunogenic epitope of the viral pp65 protein presented on HLA-A2 molecules, we directly imaged the dynamics of Ag presentation in infected cells. We demonstrate that following infection large intracellular pools of HLA-A2/pp65 complexes are localized to the Golgi. These HLA-A2/pp65 pools account for the majority of total HLA-A2 molecules in infected cells. Interestingly, these large pools are sequestered inside infected cells and only a small portion of them are exported to the cell surface. Virus-induced class I MHC down-regulation did not affect the intracellular pool of HLA-A2/pp65 complexes. Our data also suggest that proteasome function influences the release of class I complexes to the membrane. We present herein a new and direct molecular tool to study the dynamics of viral Ag presentation that may further elucidate the balance between immune response versus viral escape.

Original languageEnglish
Pages (from-to)1552-1565
Number of pages14
JournalEuropean Journal of Immunology
Volume40
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Ab
  • Ag presentation/processing
  • MHC
  • Virology

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