Cargando…
Default polyfunctional T helper 1 response to ample signal 1 alone
CD4(+) T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245500/ https://www.ncbi.nlm.nih.gov/pubmed/32313208 http://dx.doi.org/10.1038/s41423-020-0415-x |
_version_ | 1783716126238179328 |
---|---|
author | Danelli, Luca Cornish, Georgina Merkenschlager, Julia Kassiotis, George |
author_facet | Danelli, Luca Cornish, Georgina Merkenschlager, Julia Kassiotis, George |
author_sort | Danelli, Luca |
collection | PubMed |
description | CD4(+) T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited. Using cell-based vaccines, we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II (pMHC II) complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity TCR clonotypes, despite delivering intense TCR signals. In contrast to natural infection or standard vaccines, amplified signal 1, presented by a variety of professional and nonprofessional antigen-presenting cells (APCs), induced exclusively polyfunctional Th1 effector and memory cells, which protected against retroviral infection and tumor challenge, and expanded tumor-reactive CD4(+) T cells otherwise rendered unresponsive in tumor-bearing hosts. Together, our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination. |
format | Online Article Text |
id | pubmed-8245500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82455002021-07-20 Default polyfunctional T helper 1 response to ample signal 1 alone Danelli, Luca Cornish, Georgina Merkenschlager, Julia Kassiotis, George Cell Mol Immunol Article CD4(+) T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited. Using cell-based vaccines, we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II (pMHC II) complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity TCR clonotypes, despite delivering intense TCR signals. In contrast to natural infection or standard vaccines, amplified signal 1, presented by a variety of professional and nonprofessional antigen-presenting cells (APCs), induced exclusively polyfunctional Th1 effector and memory cells, which protected against retroviral infection and tumor challenge, and expanded tumor-reactive CD4(+) T cells otherwise rendered unresponsive in tumor-bearing hosts. Together, our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination. Nature Publishing Group UK 2020-04-20 2021-07 /pmc/articles/PMC8245500/ /pubmed/32313208 http://dx.doi.org/10.1038/s41423-020-0415-x Text en © CSI and USTC 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Danelli, Luca Cornish, Georgina Merkenschlager, Julia Kassiotis, George Default polyfunctional T helper 1 response to ample signal 1 alone |
title | Default polyfunctional T helper 1 response to ample signal 1 alone |
title_full | Default polyfunctional T helper 1 response to ample signal 1 alone |
title_fullStr | Default polyfunctional T helper 1 response to ample signal 1 alone |
title_full_unstemmed | Default polyfunctional T helper 1 response to ample signal 1 alone |
title_short | Default polyfunctional T helper 1 response to ample signal 1 alone |
title_sort | default polyfunctional t helper 1 response to ample signal 1 alone |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245500/ https://www.ncbi.nlm.nih.gov/pubmed/32313208 http://dx.doi.org/10.1038/s41423-020-0415-x |
work_keys_str_mv | AT danelliluca defaultpolyfunctionalthelper1responsetoamplesignal1alone AT cornishgeorgina defaultpolyfunctionalthelper1responsetoamplesignal1alone AT merkenschlagerjulia defaultpolyfunctionalthelper1responsetoamplesignal1alone AT kassiotisgeorge defaultpolyfunctionalthelper1responsetoamplesignal1alone |