TY - JOUR
T1 - The Influence of T Cell Development on Pathogen Specificity and Autoreactivity
AU - Košmrlj, Andrej
AU - Kardar, Mehran
AU - Chakraborty, Arup K.
N1 - 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.).
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Autoimmune T cells
KW - Statistical mechanics
KW - T cell pathogen specificity
KW - Thymic selection
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U2 - 10.1007/s10955-011-0403-8
DO - 10.1007/s10955-011-0403-8
M3 - Article
AN - SCOPUS:84867541881
SN - 0022-4715
VL - 149
SP - 203
EP - 219
JO - Journal of Statistical Physics
JF - Journal of Statistical Physics
IS - 2
ER -