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PMID: 23427257 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 190 ·No. 7 ·2013-04-01 ·Pages 3089-99

Borger JG, Filby A, Zamoyska R

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.

MeSH Terms
Animals Antigens/immunology CD8 Antigens/immunology,metabolism CD8-Positive T-Lymphocytes/enzymology,immunology CSK Tyrosine-Protein Kinase Cells, Cultured Enzyme Activation Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism Mice Mice, Knockout Protein Transport Proto-Oncogene Proteins c-fyn/metabolism Receptors, Antigen, T-Cell/immunology,metabolism src-Family Kinases/chemistry,metabolism
Chemicals
Antigens CD8 Antigens Receptors, Antigen, T-Cell CSK Tyrosine-Protein Kinase Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proto-Oncogene Proteins c-fyn src-Family Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Borger Jessica G
Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
Filby Andrew
Zamoyska Rose
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1202408
Published
2013-04-01
Epub
2013-00-20
Pages
3089-99
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC4595994
Subset
IM
Grants
Medical Research Council · G1100116 · United Kingdom
Wellcome Trust · 096669 · United Kingdom
Wellcome Trust · United Kingdom
Wellcome Trust · WT086054MA · United Kingdom
Medical Research Council · MC_U117512793 · United Kingdom
Medical Research Council · G1100116/1 · United Kingdom
Wellcome Trust · 086054 · United Kingdom
Wellcome Trust · 095831 · United Kingdom
External Links
PubMed source DOI: 10.4049/jimmunol.1202408 PMC Full Text View journal details
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