Abstract
T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the major histocompatibility (MHC) gene products, which are displayed on the surface of antigen presenting cells. T cells can also interact with peptide-MHC complexes, where the peptide is derived from host (self) proteins. A diverse repertoire of relatively self-tolerant T cell receptors is selected in the thymus. We study a model, computationally and analytically, to describe how thymic selection shapes the repertoire of T cell receptors, such that T cell receptor recognition of pathogenic peptides is both specific and degenerate. We also discuss the escape probability of autoimmune T cells from the thymus.
| Original language | English |
|---|---|
| Pages (from-to) | 203-219 |
| Number of pages | 17 |
| Journal | Journal of Statistical Physics |
| Volume | 149 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 2012 |
| Externally published | Yes |
Bibliographical note
Funding Information:Acknowledgements This work was supported by the Ragon Institute (A.K.C., A.K.), National Institutes of Health (NIH) Grant No. 1-PO1-AI071195-01 (A.K.C., M.K.), NSF Grant No. DMR-08-03315 (M.K.), and a NIH Director’s Pioneer award (to A.K.C.).
Funding
Acknowledgements This work was supported by the Ragon Institute (A.K.C., A.K.), National Institutes of Health (NIH) Grant No. 1-PO1-AI071195-01 (A.K.C., M.K.), NSF Grant No. DMR-08-03315 (M.K.), and a NIH Director’s Pioneer award (to A.K.C.).
| Funders | Funder number |
|---|---|
| National Science Foundation | 1206323 |
| National Institutes of Health | 1-PO1-AI071195-01 |
| Ragon Institute of MGH, MIT and Harvard |
Keywords
- Autoimmune T cells
- Statistical mechanics
- T cell pathogen specificity
- Thymic selection
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