Autoimmune Susceptibility Imposed by Public TCRβ Chains

<p>The major histocompatibility complex (MHC) is the strongest genetic risk factor for autoimmunity. It acts together with a corresponding TCR repertoire, yet, considering the extent of the repertoire's diversity, how this imposes disease susceptibility on a population is not well understood. We address the hypothesis that shared or public TCR, those present in most individuals, modulate autoimmune risk. High resolution analyses of autoimmune encephalomyelitis-associated T-cell receptor β chain (TCRβ) showed preferential utilization of public TCR sequences, implicating them in pathogenesis. Disease-associated public TCRβ, when transgenically expressed in association with endogenously rearranged T-cell receptor α chain (TCRα), could further endow unprimed T cells with autoantigen reactivity. Enforced expression of two of six public but no private TCRβ further provoked spontaneous, early-onset autoimmunity in mice. These findings implicate public TCR in skewing repertoire response characteristics and autoimmune susceptibility, demonstrate how single TCR chains can bias autoantigen specificity, and suggest that subsets of public TCR sequences may serve as diseasespecific biomarkers or therapeutic targets. </p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2014

Author dc:creator

• Zhao, Yunqian

Contributors dc:contributor

• Terrence L. Geiger, Ph.D., M.D

• autoimmunity
• EAE
• high-throughput sequencing
• public TCR repertoire
• Treg
• Diseases
• Immune System Diseases
• Medical Genetics
• Medical Immunology
• Medical Sciences
• Medicine and Health Sciences

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/317

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1322