Differential T cell receptor-mediated signaling in naive and memory CD4 T cells.
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,...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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1997
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| _version_ | 1797096470259695616 |
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| author | Farber, D Acuto, O Bottomly, K |
| author_facet | Farber, D Acuto, O Bottomly, K |
| author_sort | Farber, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:42:18Z |
| format | Journal article |
| id | oxford-uuid:d21178d0-3590-4c52-920c-4aa04097ab43 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:42:18Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:d21178d0-3590-4c52-920c-4aa04097ab432022-03-27T08:01:10ZDifferential T cell receptor-mediated signaling in naive and memory CD4 T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d21178d0-3590-4c52-920c-4aa04097ab43EnglishSymplectic Elements at Oxford1997Farber, DAcuto, OBottomly, KNaive 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. |
| spellingShingle | Farber, D Acuto, O Bottomly, K Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title | Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title_full | Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title_fullStr | Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title_full_unstemmed | Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title_short | Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. |
| title_sort | differential t cell receptor mediated signaling in naive and memory cd4 t cells |
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