English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

TCR interaction with peptide-MHC complexes triggers migration of protein kinases, actin-binding proteins, and other accessory molecules to the T cell/APC synapse. We used confocal immunofluorescence methods to show that the adapter protein LAT (linker for activation of T cells) and the guanine nucleotide exchange factor Vav also move to the APC interface in mouse CD4 T cells conjugated to anti-CD3 hybridoma cells, and in TCR-transgenic CD4 cells conjugated to APC bearing agonist (but not closely related nonagonist) peptides. The proportion of CD4+ T cells able to relocalize LAT or Vav, or to relocate cytoplasmic NT-AT (NF-ATc) from cytoplasm to nucleus, declines about 2-fold in aged mice. The decline in LAT relocalization is accompanied by a similar decline in tyrosine phosphorylation of LAT in CD4 cells stimulated by CD3/CD4 cross-linking. Two-color experiments show that LAT redistribution is strongly associated with relocalization of both NF-ATc and protein kinase C-theta among individual cells. LAT migration to the immunological synapse depends on actin polymerization as well as on activity of Src family kinases, but aging leads to only a small change in the percentage of CD4 cells that redistribute F-actin to the site of APC contact. These results suggest that defects in the ability of T cells from aged donors to move kinase substrates and coupling factors, including LAT and Vav, into the T cell/APC contact region may contribute to the decline with age in NF-ATc-dependent gene expression, and thus to defects in T cell clonal expansion.

Age-Dependent Alterations in the Assembly of Signal Transduction Complexes at the Site of T Cell/APC Interaction