| Abstract | Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. It is specific because if a T cell recognizes a particular molecular marker as “foreign”, point mutations to this marker abrogate recognition. But, at the same time, a given T cell can recognize many different pathogenic markers. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (“on” or “off”), and how this molecular machinery coupled with frustration plays a key role in designing a T cell repertoire (during development in the thymus) that recognizes antigen in a specific/degenerate fashion. |
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