Quorum sensing allows T cells to discriminate between self and nonself
T cells orchestrate pathogen-specific adaptive immune responses by identifying peptides derived from pathogenic proteins that are displayed on the surface of infected cells. Host cells also display peptide fragments from the host’s own proteins. Incorrectly identifying peptides derived from the body...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences (U.S.)
2014
|
| Online Access: | http://hdl.handle.net/1721.1/85904 https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 |
| _version_ | 1826192068493443072 |
|---|---|
| author | Butler, Thomas Charles Kardar, Mehran Chakraborty, Arup K |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Butler, Thomas Charles Kardar, Mehran Chakraborty, Arup K |
| author_sort | Butler, Thomas Charles |
| collection | MIT |
| description | T cells orchestrate pathogen-specific adaptive immune responses by identifying peptides derived from pathogenic proteins that are displayed on the surface of infected cells. Host cells also display peptide fragments from the host’s own proteins. Incorrectly identifying peptides derived from the body’s own proteome as pathogenic can result in autoimmune disease. To minimize autoreactivity, immature T cells that respond to self-peptides are deleted in the thymus by a process called negative selection. However, negative selection is imperfect, and autoreactive T cells exist in healthy individuals. To understand how autoimmunity is yet avoided, without loss of responsiveness to pathogens, we have developed a model of T-cell training and response. Our model shows that T cells reliably respond to infection and avoid autoimmunity because collective decisions made by the T-cell population, rather than the responses of individual T cells, determine biological outcomes. The theory is qualitatively consistent with experimental data and yields a criterion for thymic selection to be adequate for suppressing autoimmunity. |
| first_indexed | 2024-09-23T09:05:47Z |
| format | Article |
| id | mit-1721.1/85904 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:05:47Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/859042022-09-26T10:25:15Z Quorum sensing allows T cells to discriminate between self and nonself Butler, Thomas Charles Kardar, Mehran Chakraborty, Arup K Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Physics Ragon Institute of MGH, MIT and Harvard Butler, Thomas Charles Kardar, Mehran Chakraborty, Arup K. T cells orchestrate pathogen-specific adaptive immune responses by identifying peptides derived from pathogenic proteins that are displayed on the surface of infected cells. Host cells also display peptide fragments from the host’s own proteins. Incorrectly identifying peptides derived from the body’s own proteome as pathogenic can result in autoimmune disease. To minimize autoreactivity, immature T cells that respond to self-peptides are deleted in the thymus by a process called negative selection. However, negative selection is imperfect, and autoreactive T cells exist in healthy individuals. To understand how autoimmunity is yet avoided, without loss of responsiveness to pathogens, we have developed a model of T-cell training and response. Our model shows that T cells reliably respond to infection and avoid autoimmunity because collective decisions made by the T-cell population, rather than the responses of individual T cells, determine biological outcomes. The theory is qualitatively consistent with experimental data and yields a criterion for thymic selection to be adequate for suppressing autoimmunity. National Institutes of Health (U.S.). Pioneer Award National Science Foundation (U.S.) (Grant 12-06323) 2014-03-24T16:02:57Z 2014-03-24T16:02:57Z 2013-07 2012-12 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/85904 Butler, T. C., M. Kardar, and A. K. Chakraborty. “Quorum Sensing Allows T Cells to Discriminate Between Self and Nonself.” Proceedings of the National Academy of Sciences 110, no. 29 (July 16, 2013): 11833–11838. https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 en_US http://dx.doi.org/10.1073/pnas.1222467110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Butler, Thomas Charles Kardar, Mehran Chakraborty, Arup K Quorum sensing allows T cells to discriminate between self and nonself |
| title | Quorum sensing allows T cells to discriminate between self and nonself |
| title_full | Quorum sensing allows T cells to discriminate between self and nonself |
| title_fullStr | Quorum sensing allows T cells to discriminate between self and nonself |
| title_full_unstemmed | Quorum sensing allows T cells to discriminate between self and nonself |
| title_short | Quorum sensing allows T cells to discriminate between self and nonself |
| title_sort | quorum sensing allows t cells to discriminate between self and nonself |
| url | http://hdl.handle.net/1721.1/85904 https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 |
| work_keys_str_mv | AT butlerthomascharles quorumsensingallowstcellstodiscriminatebetweenselfandnonself AT kardarmehran quorumsensingallowstcellstodiscriminatebetweenselfandnonself AT chakrabortyarupk quorumsensingallowstcellstodiscriminatebetweenselfandnonself |