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B.S., Duke University, Durham, NC. 2012
A diverse repertoire of T cells allows for the recognition of a large variety of pathogens. Their development in the thymus requires selection events based on their T cell receptor (TCR) specificities – namely, the signaling strength through these receptors. Diversity comes with the potential for self-reactivity and autoimmunity. T cells that bear TCRs that recognize self-antigens can be eliminated by clonal deletion. My project will examine the T cell repertoire that is deleted early in negative selection in the thymic cortex and compare these to clones deleted late in negative selection in the thymic medulla. Such repertoire analysis will show if the antigens being presented and selected against in the two regions of the thymus are non-overlapping. To do so, we will be using a fixed TCRβ model with diverse α chains to drive development of thymocytes that express TCRs that are normally deleted in either stage of negative selection.
Wiesner, D.L., C.A. Specht, C.K. Lee, K.D. Smith, L. Mukaremera, S.T. Lee, J.A. Elias, J.N. Nielsen, D.R. Boulware, P.R. Bohjanen, M.K. Jenkins, S.M. Levitz and K. Nielsen. 2015. Chitin recognition via chitotriosidase promotes pathogenic type-2 helper T cell responses to cryptococcal infection. PLoS Pathog. 11(3): e1004701.