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Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine-phosphorylated protein species overall and phosphorylating the T cell-specific ZAP-70 tyrosine kinase which is recruited to the CD3zeta subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine-phosphorylated substrates and fail to phosphorylate ZAP-70, yet unphosphorylated ZAP-70 can associate with the TCR/CD3 complex. Moreover, a 26/28-kDa phosphorylated doublet is associated with CD3zeta in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP-70 and CD3-associated proteins, the ZAP-70-related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP-70 in memory CD4 T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.

Original publication

DOI

10.1002/eji.1830270838

Type

Journal article

Journal

Eur J Immunol

Publication Date

08/1997

Volume

27

Pages

2094 - 2101

Keywords

Amino Acid Sequence, Animals, Antibodies, Monoclonal, CD3 Complex, CD4-Positive T-Lymphocytes, Enzyme Precursors, Female, Immunologic Memory, In Vitro Techniques, Intracellular Signaling Peptides and Proteins, Mice, Mice, Inbred BALB C, Peptide Fragments, Phosphorylation, Protein-Tyrosine Kinases, Receptors, Antigen, T-Cell, Signal Transduction, Syk Kinase, T-Lymphocyte Subsets, Tyrosine, Vanadates, ZAP-70 Protein-Tyrosine Kinase