title: Differential polarization of C-terminal Src kinase between naive and antigen-experienced CD8+ T cells.
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.
authors: Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors: Jessica G
authors: JG
authors: Borger
authors: Andrew
authors: A
authors: Filby
authors: Rose
authors: R
authors: Zamoyska
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D000081247:CSK Tyrosine-Protein Kinase; D002478:Cells, Cultured; D004789:Enzyme Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000941:Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D000081247:CSK Tyrosine-Protein Kinase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases