Merkenschlager, JE; (2016) Clonal Selection in CD4 T cells: the role of TCR specificity and avidity. Doctoral thesis , UCL (University College London).

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Abstract

The ability to distinguish self from nonself is a fundamental property of the innate and adaptive immune system. For the somatically generated repertoire of T cell and B cell antigen receptors (TCR and BCR, respectively), self–nonself discrimination is primarily achieved through clonal deletion of lymphocytes expressing strongly auto-reactive receptors. Removal of such receptors from the TCR and BCR repertoires causes irreversible self-tolerance. For a T cell, this is a precarious life. During development in the thymus it must adopt a certain degree of self-reactivity in order to pass selection criteria, yet this must fall below a threshold, which would flag it to be negatively selected. This rigorous purging sees only approximately 3-5% of candidate thymocytes making it through the process. Once in the periphery, the quality of TCR signaling continues to be important and is heavily censored by extrinsic factors, which actively shape and condition both the pre-immune and antigen-responding repertoire. Although it is very clear that the signaling capacity of the TCR, whether this be towards self or nonself, is a key determinant in defining the trajectory of a T cell, the degree to which it governs these fate decisions remains ill defined. This thesis examines the relationship that exists between the T cell and its TCR throughout the life of a T cell.

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