Abstract
The biochemical processing of and Ag presentation by MHC class II molecules were examined in B cell lines derived from pairs of identical twins discordant for type 1 diabetes. MHC class II defects detected exclusively in cells derived from the twins with autoimmunity included increased rates of transport to and subsequent turnover at the cell surface, inadequate glycosylation, and a reduced display at the cell surface of antigenic peptides. These defects appeared to be secondary to a decreased abundance of the p35 isoform of the invariant chain (Ii), a human-specific chaperone protein for MHC class II normally generated by use of an alternative translation start site. Stable transfection of diabetic B cell lines with an Ii p35 expression vector corrected the defects in MHC class II processing and peptide presentation. A defect in the expression of Ii p35 may thus result in impairment of Ag presentation by MHC class II molecules and thereby contribute to the development of type 1 diabetes in at-risk genotypes.
Publication types
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Research Support, Non-U.S. Gov't
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Twin Study
MeSH terms
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Amino Acid Sequence
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Antigen Presentation* / genetics
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Line, Transformed
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Cell Membrane / genetics
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / metabolism
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Diseases in Twins* / genetics
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum / immunology
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Endoplasmic Reticulum / metabolism
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Histocompatibility Antigens Class II / biosynthesis
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism*
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Humans
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Membrane Proteins / biosynthesis
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Molecular Sequence Data
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Peptides / genetics
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Peptides / metabolism
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Protein Binding / genetics
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Protein Binding / immunology
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Protein Processing, Post-Translational / genetics
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Protein Processing, Post-Translational / immunology*
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Protein Transport / genetics
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Protein Transport / immunology
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Time Factors
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Transfection
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Twins, Monozygotic / genetics
Substances
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Antigens, Differentiation, B-Lymphocyte
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Histocompatibility Antigens Class II
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Membrane Proteins
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Peptides
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invariant chain