Journal article

Ubiquitination of MHC Class II Is Required for Development of Regulatory but Not Conventional CD4( ) T Cells

Haiyin Liu, Kayla R Wilson, Patrick Schriek, Christophe Macri, Annabelle B Blum, Lauren Francis, Melanie Heinlein, Champa Nataraja, James Harris, Sarah A Jones, Daniel HD Gray, Jose A Villadangos, Justine D Mintern

The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2020

Abstract

MHC class II (MHC II) displays peptides at the cell surface, a process critical for CD4+ T cell development and priming. Ubiquitination is a mechanism that dictates surface MHC II with the attachment of a polyubiquitin chain to peptide-loaded MHC II, promoting its traffic away from the plasma membrane. In this study, we have examined how MHC II ubiquitination impacts the composition and function of both conventional CD4+ T cell and regulatory T cell (Treg) compartments. Responses were examined in two models of altered MHC II ubiquitination: MHCIIKRKI/KI mice that express a mutant MHC II unable to be ubiquitinated or mice that lack membrane-associated RING-CH 8 (MARCH8), the E3 ubiquitin liga..

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Grants

Awarded by National Health and Medical Research Council, Department of Health Australia


Awarded by Australian Research Council, Department of Education and Training grants or fellowships


Awarded by Human Frontiers Science Program


Funding Acknowledgements

This work was supported by National Health and Medical Research Council, Department of Health Australia grants or fellowships (1078763, 1158024, 1121325, and 1145888 [to D.H.D.G.], 1058193, 1154502, 1016629, and 1163090 [to J.A.V.], and 1161101 and 1129672 [to J.D.M.]), Australian Research Council, Department of Education and Training grants or fellowships (110101383 and 160103134 [to J.A.V.] and 190101242, 180100844, 160101373, and 180100521 [to J.D.M.]), a Human Frontiers Science Program grant (0064/2011 [to J.A.V.]), and the Victorian State Government Operational Infrastructure Support and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government National Health and Medical Research Council.