The influence of T cell development on pathogen specificity and autoreactivity

• Main Authors: Kosmrlj, Andrej (Author), Kardar, Mehran (Contributor), Chakraborty, Arup K. (Contributor)
• Other Authors: Institute for Medical Engineering and Science (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Massachusetts Institute of Technology. Department of Physics (Contributor), Ragon Institute of MGH, MIT and Harvard (Contributor)
• Format: Article
• Language: English
• Published: Springer-Verlag, 2013-03-21T16:09:06Z.
• Subjects: Article
• Online Access: Get fulltext

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.
Ragon Institute of MGH, MIT and Harvard
National Institutes of Health (U.S.) (Grant 1-PO1-AI071195-01)
National Science Foundation (U.S.) (Grant DMR-08-03315)
National Institutes of Health (U.S.). Pioneer Award