Journal article
Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells
JD Ooi, J Petersen, YH Tan, M Huynh, ZJ Willett, SH Ramarathinam, PJ Eggenhuizen, KL Loh, KA Watson, PY Gan, MA Alikhan, NL Dudek, A Handel, BG Hudson, L Fugger, DA Power, SG Holt, PT Coates, JW Gregersen, AW Purcell Show all
Nature | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/nature22329
Abstract
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4+ T-cell selfepitope derived from the a3 chain of type IV collagen (a3135-145)1-4. While HLA-DR15 confers a markedly increased disease risk, the protective HLA-DR1 allele is dominantly protective in trans with HLA-DR15 (ref. 2). We show that autoreact..
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Grants
Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
We thank the staff of the Australian Synchrotron (beamline MX1 and MX2) for assistance with data collection and donors of the Australian Bone Marrow Donor Registry for blood samples. This study was supported by grants from the National Health and Medical Research Council of Australia (NHMRC), 1048575 and 1079648 to A.R.K., 334067 to A.R.K. and S.R.H., and 1071916 to N.L.L.G. N.L.L.G. is supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship. A.W.P. is supported by an NHMRC Senior Research Fellowship. J.R. is supported by an Australian Research Council Laureate Fellowship.