Peptide-specific intercellular transfer of MHC class II to CD4+ T cells directly from the immunological synapse upon cellular dissociation

Scott A. Wetzel, Timothy W. McKeithan, David C. Parker

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The transfer of membrane proteins from APC to T cells was initially described in the 1970s, and subsequent work has described two mechanisms of transfer: APC-derived exosomes and direct transfer of small packets, while cells remain conjugated. Using fibroblast APC expressing a GFP-tagged I-Ek molecule with covalently attached antigenic peptide, we observed a third mechanism in live cell imaging: T cells spontaneously dissociating from APC often capture MHC:peptide complexes directly from the immunological synapse. Using two I-Ek-restricted marine TCR transgenic T cells with different peptide specificity, we show in this study that the MHC transfer is peptide specific. Using blocking Abs, we found that MHC:peptide transfer in this system requires direct TCR-MHC:peptide interactions and is augmented by costimulation through CD28-CD80 interactions. Capture of the GFP-tagged MHC:peptide complexes correlates with an activated phenotype of the T cell, elevated CD69 with down-modulated TCR. The transferred MHC:peptide molecules transferred to the T cell are associated with molecules that imply continued TCR signaling; p56lck, phosphotyrosine, and polarization of the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)80-89
Number of pages10
JournalJournal of Immunology
Volume174
Issue number1
DOIs
StatePublished - Jan 1 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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