Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity.

Autor:	Ito Y; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA., Ashenberg O; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA., Pyrdol J; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA., Luoma AM; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA., Rozenblatt-Rosen O; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA., Hofree M; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA., Christian E; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA., Ferrari de Andrade L; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA., Tay RE; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA., Teyton L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA., Regev A; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA., Dougan SK; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA stephanie_dougan@dfci.harvard.edu.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA., Wucherpfennig KW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA kai_wucherpfennig@dfci.harvard.edu.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2018 Oct 01; Vol. 215 (10), pp. 2617-2635. Date of Electronic Publication: 2018 Sep 05.
DOI:	10.1084/jem.20180300
Abstrakt:	A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-A g7 even in the absence of DM, and this property is related to the type 1 diabetes-associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-A g7 These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. Rapid CLIP dissociation enhanced the presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen-processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition. (© 2018 Ito et al.)
Databáze:	MEDLINE
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