Rapid CLIP Dissociation from MHC II Promotes an Unusual Antigen Presentation Pathway in Autoimmunity
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ABSTRACT:
PROVIDER: PRJNA485179 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7661420_1.fastq.gz | Fastqsanger.gz | |||
| SRR7661420_2.fastq.gz | Fastqsanger.gz | |||
| SRR7661430_1.fastq.gz | Fastqsanger.gz | |||
| SRR7661430_2.fastq.gz | Fastqsanger.gz | |||
| SRR7661440_1.fastq.gz | Fastqsanger.gz |
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Project description: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-Ag7 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-Ag7 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.
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