Classical MHC expression by DP thymocytes impairs the selection of non-classical MHC restricted innate-like T cells

Hristo Georgiev, Changwei Peng, Matthew A. Huggins, Stephen C. Jameson and Kristin A. Hogquist ()
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Hristo Georgiev: University of Minnesota
Changwei Peng: University of Minnesota
Matthew A. Huggins: University of Minnesota
Stephen C. Jameson: University of Minnesota
Kristin A. Hogquist: University of Minnesota

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Conventional T cells are selected by peptide-MHC expressed by cortical epithelial cells in the thymus, and not by cortical thymocytes themselves that do not express MHC I or MHC II. Instead, cortical thymocytes express non-peptide presenting MHC molecules like CD1d and MR1, and promote the selection of PLZF+ iNKT and MAIT cells, respectively. Here, we report an inducible class-I transactivator mouse that enables the expression of peptide presenting MHC I molecules in different cell types. We show that MHC I expression in DP thymocytes leads to expansion of peptide specific PLZF+ innate-like (PIL) T cells. Akin to iNKT cells, PIL T cells differentiate into three functional effector subsets in the thymus, and are dependent on SAP signaling. We demonstrate that PIL and NKT cells compete for a narrow niche, suggesting that the absence of peptide-MHC on DP thymocytes facilitates selection of non-peptide specific lymphocytes.

Date: 2021
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DOI: 10.1038/s41467-021-22589-z

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