Influence of correlated antigen presentation on T-cell negative selection in the thymus
The thymus is the primary organ for the generation of naive T cells, a key component of the immune system. Tolerance of T cells to self is achieved primarily in the thymic medulla, where immature T cells (thymocytes) sample self-peptides presented by medullary thymic epithelial cells (mTECs). A suff...
| Main Authors: | , |
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| Format: | Journal article |
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Royal Society
2018
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| _version_ | 1797103415538483200 |
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| author | Banerjee, S Chapman, SJ |
| author_facet | Banerjee, S Chapman, SJ |
| author_sort | Banerjee, S |
| collection | OXFORD |
| description | The thymus is the primary organ for the generation of naive T cells, a key component of the immune system. Tolerance of T cells to self is achieved primarily in the thymic medulla, where immature T cells (thymocytes) sample self-peptides presented by medullary thymic epithelial cells (mTECs). A sufficiently strong interaction activates the thymocytes leading to negative selection. A key question of current interest is whether there is any structure in the manner in which mTECs present peptides: can any mTEC present any peptide at any time, or are there particular patterns of correlated peptide presentation? We investigate this question using a mathematical model of negative selection. We find that correlated patterns of peptide presentation may be advantageous in negatively selecting low-degeneracy thymocytes (that is, those thymocytes which respond to relatively few peptides). We also quantify the probability that an auto-reactive thymocyte exits the thymus before it encounters a cognate antigen. The results suggest that heterogeneity of gene co-expression in mTECs has an effect on the probability of escape of autoreactive thymocytes. |
| first_indexed | 2024-03-07T06:19:51Z |
| format | Journal article |
| id | oxford-uuid:f25cb724-ad2b-47f7-a5dd-8d03bc0478b5 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:19:51Z |
| publishDate | 2018 |
| publisher | Royal Society |
| record_format | dspace |
| spelling | oxford-uuid:f25cb724-ad2b-47f7-a5dd-8d03bc0478b52022-03-27T12:03:08ZInfluence of correlated antigen presentation on T-cell negative selection in the thymusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f25cb724-ad2b-47f7-a5dd-8d03bc0478b5Symplectic Elements at OxfordRoyal Society2018Banerjee, SChapman, SJThe thymus is the primary organ for the generation of naive T cells, a key component of the immune system. Tolerance of T cells to self is achieved primarily in the thymic medulla, where immature T cells (thymocytes) sample self-peptides presented by medullary thymic epithelial cells (mTECs). A sufficiently strong interaction activates the thymocytes leading to negative selection. A key question of current interest is whether there is any structure in the manner in which mTECs present peptides: can any mTEC present any peptide at any time, or are there particular patterns of correlated peptide presentation? We investigate this question using a mathematical model of negative selection. We find that correlated patterns of peptide presentation may be advantageous in negatively selecting low-degeneracy thymocytes (that is, those thymocytes which respond to relatively few peptides). We also quantify the probability that an auto-reactive thymocyte exits the thymus before it encounters a cognate antigen. The results suggest that heterogeneity of gene co-expression in mTECs has an effect on the probability of escape of autoreactive thymocytes. |
| spellingShingle | Banerjee, S Chapman, SJ Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title | Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title_full | Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title_fullStr | Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title_full_unstemmed | Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title_short | Influence of correlated antigen presentation on T-cell negative selection in the thymus |
| title_sort | influence of correlated antigen presentation on t cell negative selection in the thymus |
| work_keys_str_mv | AT banerjees influenceofcorrelatedantigenpresentationontcellnegativeselectioninthethymus AT chapmansj influenceofcorrelatedantigenpresentationontcellnegativeselectioninthethymus |