MHC II regulation of CD8+ T cell tolerance and implications in autoimmunity and cancer immunotherapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1029940 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26439023_1.fastq.gz | Fastqsanger.gz | |||
| SRR26439023_2.fastq.gz | Fastqsanger.gz | |||
| SRR26439024_1.fastq.gz | Fastqsanger.gz | |||
| SRR26439024_2.fastq.gz | Fastqsanger.gz | |||
| SRR26439025_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 b57 polymorphism. We generated knock-in Non-obese Diabetic (NOD) mice with a single amino acid change in the CLIP segment of 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 b cell secretory granules. Rapid CLIP dissociation enhanced 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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