Attenuated T cell responses to a high-potency ligand in vivo Journal Article
| Authors: | Corse, E.; Gottschalk, R. A.; Krogsgaard, M.; Allison, J. P. |
| Article Title: | Attenuated T cell responses to a high-potency ligand in vivo |
| Abstract: | αβ T cell receptor (TCR) recognition of foreign peptides bound to major histocompatibility complex (pMHC) molecules on the surface of antigen presenting cells is a key event in the initiation of adaptive cellular immunity. In vitro, high-affinity binding and/or long-lived interactions between TCRs and pMHC correlate with high-potency T cell activation. However, less is known about the influence of TCR/pMHC interaction parameters on T cell responses in vivo. We studied the influence of TCR/pMHC binding characteristics on in vivo T cell immunity by tracking CD4+ T cell activation, effector, and memory responses to immunization with peptides exhibiting a range of TCR/pMHC half-lives and in vitro T cell activation potencies. Contrary to predictions from in vitro studies, we found that optimal in vivo T cell responses occur to ligands with intermediate TCR/pMHC half-lives. The diminished in vivo responses we observed to the ligand exhibiting the longest TCR/pMHC half-life were associated with attenuation of intracellular signaling, expansion, and function over a broad range of time points. Our results reveal a level of control over T cell activation in vivo not recapitulated in in vitro assays and highlight the importance of considering in vivo efficacy of TCR ligands as part of vaccine design. © 2010 Corse et al. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; binding affinity; t lymphocyte; animal cell; mouse; animal experiment; in vivo study; peptide; drug design; prediction; drug receptor binding; t lymphocyte receptor beta chain; lymphocyte activation; cellular immunity; cd4+ t lymphocyte; cd4-positive t-lymphocytes; ligand; ligands; effector cell; major histocompatibility complex; half life time; cell expansion; t lymphocyte activation; vaccine; receptors, antigen, t-cell, alpha-beta; lymphocyte function; immunization; t lymphocyte receptor alpha chain; memory t lymphocyte; peptide 102s; peptide k3; peptide k5; peptide mcc |
| Journal Title: | PLoS Biology |
| Volume: | 8 |
| Issue: | 9 |
| ISSN: | 1544-9173 |
| Publisher: | Public Library of Science |
| Date Published: | 2010-09-01 |
| Start Page: | e1000481 |
| Language: | English |
| DOI: | 10.1371/journal.pbio.1000481 |
| PUBMED: | 20856903 |
| PROVIDER: | scopus |
| PMCID: | PMC2939023 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "Article No. e1000481" - "CODEN: PBLIB" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work