Differential polarization of C-terminal Src kinase between naive and antigen-experienced CD8+ T cells

Jessica G. Borger, Andrew Filby, Rose Zamoyska

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

In CD8+ T cells, engagement of the TCR with agonist peptide:MHC molecules causes dynamic redistribution of surface molecules including the CD8 coreceptor to the immunological synapse. CD8 associates with the Src-family kinase (SFK) Lck, which, in turn, initiates the rapid tyrosine phosphorylation events that drive cellular activation. Compared with naive T cells, Ag-experienced CD8+ T cells make shorter contacts with APC, are less dependent on costimulation, and are triggered by lower concentrations of Ag, yet the molecular basis of this more efficient response of memory T cells is not fully understood. In this article, we show differences between naive and Ag-experienced CD8+ T cells in colocalization of the SFKs and their negative regulator, C-terminal Src kinase (Csk). In naive CD8+ T cells, there was pronounced colocalization of SFKs and Csk at the site of TCR triggering, whereas in Ag-experienced cells, Csk displayed a bipolar distribution with a proportion of the molecules sequestered within a cytosolic area in the distal pole of the cell. The data show that there is differential redistribution of a key negative regulator away from the site of TCR engagement in Ag-experienced CD8+ T cells, which might be associated with the more efficient responses of these cells on re-exposure to Ag.

Original languageEnglish
Pages (from-to)3089-3099
Number of pages11
JournalJournal of Immunology
Volume190
Issue number7
DOIs
Publication statusPublished - 1 Apr 2013
Externally publishedYes

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