15 February 2008
Arup Chakraborty
Laboratory for Computational Immunology
Departments of Chemistry, Chemical and Biological Engineering
MIT
The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). They express T cell receptor (TCR) molecules on their surface, which recognize molecular signatures of pathogens. Each T cell expresses a distinct TCR, which can bind to short peptides (p) derived from pathogenic proteins associated with products of the major histocompatibility (MHC) genes; these pMHC molecules are expressed on antigen presenting cells. Sufficiently strong TCR-pMHC binding results in T cell activation. TCR bind weakly to endogenous pMHC molecules, thereby preventing frequent autoimmune responses. After briefly outlining how T cells detect minute numbers of pathogen-derived pMHC molecules, I will focus on how the specific, diverse, and self-tolerant T cell repertoire is designed in the thymus. I will detail how an approach that brings together theoretical and computational studies (rooted in statistical physics) with genetic, biochemical, and imaging experiments has allowed us to shed light on the pertinent mechanistic principles.