Title

HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet beta-Cells From Donors With Type 1 Diabetes

UMMS Affiliation

Program in Molecular Medicine, Diabetes Center of Excellence; Division of Diabetes, Department of Medicine; Program in Bioinformatics and Integrative Biology; Garber Lab

Publication Date

2019-05-01

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Computational Biology | Endocrine System Diseases | Genetic Phenomena | Immune System Diseases | Immunopathology | Integrative Biology | Nucleic Acids, Nucleotides, and Nucleosides | Nutritional and Metabolic Diseases | Systems Biology

Abstract

Type 1 diabetes studies consistently generate data showing islet beta-cell dysfunction and T cell-mediated anti-beta-cell-specific autoimmunity. To explore the pathogenesis, we interrogated the beta-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single beta-cells. Consistent with immunohistological studies, beta-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species. These beta-cells also expressed mRNA for Class II and Class II antigen presentation pathway components, but lacked the macrophage marker CD68. Immunohistological study of three independent cohorts of donors with recent-onset type 1 diabetes showed Class II protein and its transcriptional regulator Class II MHC trans-activator protein expressed by a subset of insulin(+)CD68(-) beta-cells, specifically found in islets with lymphocytic infiltrates. beta-Cell surface expression of HLA Class II was detected on a portion of CD45(-)insulin(+) beta-cells from donors with type 1 diabetes by immunofluorescence and flow cytometry. Our data demonstrate that pancreatic beta-cells from donors with type 1 diabetes express Class II molecules on selected cells with other key genes in those pathways and inflammation-associated genes. beta-Cell expression of Class II molecules suggests that beta-cells may interact directly with islet-infiltrating CD4(+) T cells and may play an immunopathogenic role.

DOI of Published Version

10.2337/db18-0686

Source

Diabetes. 2019 May;68(5):988-1001. doi: 10.2337/db18-0686. Epub 2019 Mar 4. Link to article on publisher's site

Journal/Book/Conference Title

Diabetes

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30833470

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