Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 + T Cells Across MHC Class I Restrictions in Humans and NOD Mice.

Autor:	Azoury ME; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Tarayrah M; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Afonso G; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Pais A; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Colli ML; Université Libre de Bruxelles Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium., Maillard C; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Lavaud C; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Alexandre-Heymann L; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.; Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires de Paris Centre-Université de Paris, Cochin Hospital, Service de Diabétologie et Immunologie Clinique, Paris, France., Gonzalez-Duque S; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.; École Supérieure de Physique et de Chimie Industrielles Paris, Université Paris Sciences et Lettres, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, Paris, France., Verdier Y; École Supérieure de Physique et de Chimie Industrielles Paris, Université Paris Sciences et Lettres, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, Paris, France., Vinh J; École Supérieure de Physique et de Chimie Industrielles Paris, Université Paris Sciences et Lettres, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, Paris, France., Pinto S; Division of Developmental Immunology, Deutsches Krebsforschungszentrum, Heidelberg, Germany., Buus S; Laboratory of Experimental Immunology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Dubois-Laforgue D; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.; Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires de Paris Centre-Université de Paris, Cochin Hospital, Service de Diabétologie et Immunologie Clinique, Paris, France., Larger E; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.; Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires de Paris Centre-Université de Paris, Cochin Hospital, Service de Diabétologie et Immunologie Clinique, Paris, France., Beressi JP; Service de Diabétologie, Centre Hospitalier de Versailles André Mignot, Le Chesnay, France., Bruno G; Department of Medical Sciences, University of Turin, Turin, Italy., Eizirik DL; Université Libre de Bruxelles Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium., You S; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Mallone R; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France roberto.mallone@inserm.fr.; Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires de Paris Centre-Université de Paris, Cochin Hospital, Service de Diabétologie et Immunologie Clinique, Paris, France.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2020 Dec; Vol. 69 (12), pp. 2678-2690. Date of Electronic Publication: 2020 Sep 14.
DOI:	10.2337/db20-0013
Abstrakt:	The antigenic peptides processed by β-cells and presented through surface HLA class I molecules are poorly characterized. Each HLA variant (e.g., the most common being HLA-A2 and HLA-A3) carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of the HLA-A2/A3 peptidome of β-cells, we analyzed the HLA-A3-restricted peptides targeted by circulating CD8 + T cells. Several peptides were recognized by CD8 + T cells within a narrow frequency (1-50/10 6 ), which was similar in donors with and without type 1 diabetes and harbored variable effector/memory fractions. These epitopes could be classified as conventional peptides or neoepitopes, generated either via peptide cis -splicing or mRNA splicing (e.g., secretogranin-5 [SCG5]-009). As reported for HLA-A2-restricted peptides, several epitopes originated from β-cell granule proteins (e.g., SCG3, SCG5, and urocortin-3). Similarly, H-2K d -restricted CD8 + T cells recognizing the murine orthologs of SCG5, urocortin-3, and proconvertase-2 infiltrated the islets of NOD mice and transferred diabetes into NOD/ scid recipients. The finding of granule proteins targeted in both humans and NOD mice supports their disease relevance and identifies the insulin granule as a rich source of epitopes, possibly reflecting its impaired processing in type 1 diabetes. (© 2020 by the American Diabetes Association.)
Databáze:	MEDLINE
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