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; Kris Hogquist

doi:10.1038/s41467-021-22589-z

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, Kris Hogquist

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13 Scopus citations

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.

Original language	English (US)
Article number	2308
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22589-z
State	Published - Dec 1 2021

Bibliographical note

Funding Information:
We thank all the present and past members of the Jamequist lab and members of the Center for Immunology at the University of Minnesota for the inspiring discussions and assistance. We also thank Dr. Günter Bernhardt and Dr. Nadine Eckert for critically reviewing the manuscript. This work benefitted from data assembled by the ImmGen consortium. This work was supported by DFG fellowship GE 3062/1-1 to H.G. and by NIH grant R37 AI039560 to K.A.H.

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© 2021, The Author(s).

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

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.",

author = "Hristo Georgiev and Changwei Peng and Huggins, {Matthew A.} and Jameson, {Stephen C.} and Kris Hogquist",

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AU - Jameson, Stephen C.

AU - Hogquist, Kris

N1 - Funding Information: We thank all the present and past members of the Jamequist lab and members of the Center for Immunology at the University of Minnesota for the inspiring discussions and assistance. We also thank Dr. Günter Bernhardt and Dr. Nadine Eckert for critically reviewing the manuscript. This work benefitted from data assembled by the ImmGen consortium. This work was supported by DFG fellowship GE 3062/1-1 to H.G. and by NIH grant R37 AI039560 to K.A.H. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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

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