MHC class II ubiquitination regulates dendritic cell function and immunity

KR Wilson; D Jenika; AB Blum; C Macri; B Xu; H Liu; P Schriek; D Schienstock; L Francis; FV Makota; S Ishido; SN Mueller; MH Lahoud; I Caminschi; LE Edgington-Mitchell; JA Villadangos; JD Mintern

Journal article

MHC class II ubiquitination regulates dendritic cell function and immunity

KR Wilson, D Jenika, AB Blum, C Macri, B Xu, H Liu, P Schriek, D Schienstock, L Francis, FV Makota, S Ishido, SN Mueller, MH Lahoud, I Caminschi, LE Edgington-Mitchell, JA Villadangos, JD Mintern

Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2021

DOI: 10.4049/jimmunol.2001426

Abstract

MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4+ T cell immunity. Cell surface levels of MHC II loaded with peptide is controlled by ubiquitination. In this study, we have examined how MHC II ubiquitination impacts immunity using MHC IIKRKI/KI mice expressing mutant MHC II molecules that are unable to be ubiquitinated. Numbers of conventional DC (cDC) 1, cDC2 and plasmacytoid DCs were significantly reduced in MHC IIKRKI/KI spleen, with the remaining MHC IIKRKI/KI DCs expressing an altered surface phenotype. Whereas Ag uptake, endosomal pH, and cathepsin protease activity were unaltered, MHC IIKRKI/KI cDC1 produced increased inflammatory cytokines and posses..

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University of Melbourne Researchers

Kayla Wilson Author

Devi Jenika Author

CHRISTOPHE MACRI Author

Scott Mueller Author

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Grants

Awarded by University of Melbourne

Funding Acknowledgements

This work was supported by Department of Health Australia, National Health and Medical Research Council grants or fellowships 1058193, 1113293, 1154502, and 1163090 (to J.A.V.) and 1161101 and 1129672 (to J.D.M.), Department of Education and Training, Australian Research Council (ARC) grants or fellowships 160103134, 170102471, and 190102213 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 Australian Government's National Health and Medical Research Council Victorian State Government Operational Infrastructure Support and the Independent Research Institutes Infrastructure Support Scheme. L.E.E.-M. was supported by the Russell and Mab Grimwade Miegunyah Fund, funded at the University of Melbourne, which supplied a Grimwade Fellowship, and an ARC Discovery Early Career Researcher Award Fellowship (ARC, DE180100418).