Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses Journal Article
| Authors: | Gottschalk, R. A.; Hathorn, M. M.; Beuneu, H.; Corse, E.; Dustin, M. L.; Altan-Bonnet, G.; Allison, J. P. |
| Article Title: | Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses |
| Abstract: | The strength of T-cell receptor (TCR) stimulation and subsequent T-cell response depend on a combination of peptide-major histocompatibility complex (pMHC) density and potency. By comparing two different pMHC at doses yielding similar proliferation in vivo, we have highlighted unexpected differences in the qualitative and quantitative effects of TCR ligand. Measurements of cytokine sensitivity and two-photon imaging of T cell-dendritic cell (T-DC) interactions reveal discrimination between comparably weak stimuli resulting from either decreased pMHC potency or pMHC density. In addition, TCR-induced genes in broad gene expression profiles segregate into two groups: one that responds to cumulative TCR signal and another that responds to pMHC quality, independent of quantity. These observations suggest that models of TCR ligand discrimination must account for disparate sensitivity of downstream responses to specific influences of pMHC potency. |
| Keywords: | signal transduction; controlled study; protein expression; protein phosphorylation; nonhuman; transcription factor foxp3; lymphocyte proliferation; t lymphocyte; animal cell; mouse; interleukin 2; gene expression profiling; dendritic cell; animal experiment; in vivo study; t lymphocyte receptor; quantitative analysis; cytokine production; down regulation; upregulation; gene induction; cytotoxic t lymphocyte antigen 4; major histocompatibility complex; stat5 protein; cell interaction; t lymphocyte activation; protein tyrosine phosphatase shp 2; il-2; interleukin 2 receptor alpha; qualitative analysis; cd69 antigen; l selectin; interleukin 2 receptor beta; affinity; rgs protein; stat5; dual specificity phosphatase 6 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 109 |
| Issue: | 3 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2012-01-17 |
| Start Page: | 881 |
| End Page: | 886 |
| Language: | English |
| DOI: | 10.1073/pnas.1119763109 |
| PROVIDER: | scopus |
| PMCID: | PMC3271915 |
| PUBMED: | 22223661 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: PNASA" - "Source: Scopus" |
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130Allison -
42Altan-Bonnet -
10Corse -
3
Hathorn
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