Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates

Author:

Lebel Marie-ÈveORCID,Coutelier MarieORCID,Galipeau MariaORCID,Kleinman Claudia L.ORCID,Moon James J.ORCID,Melichar Heather J.ORCID

Abstract

AbstractMedullary thymic epithelial cells (mTEC) contribute to the development of T cell tolerance by expressing and presenting tissue-restricted antigens (TRA), so that developing T cells can assess the self-reactivity of their antigen receptors prior to leaving the thymus. mTEC are a heterogeneous population of cells that differentially express TRA. Whether mTEC subsets induce distinct autoreactive T cell fates remains unclear. Here, we establish bacterial artificial chromosome (BAC)-transgenic mouse lines with biased mTEClo or mTEChi expression of model antigens. The transgenic lines support negative selection of antigen-specific thymocytes depending on antigen dose. However, model antigen expression predominantly by mTEClo supports TCRαβ+ CD8αα intraepithelial lymphocyte development; meanwhile, mTEChi-restricted expression preferentially induces Treg differentiation of antigen-specific cells in these models to impact control of infectious agents and tumor growth. In summary, our data suggest that mTEC subsets may have a function in directing distinct mechanisms of T cell tolerance.

Funder

Gouvernement du Canada | Canadian Institutes of Health Research

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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