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iCLIP - Transcriptome-wide Mapping of Protein-RNA Interactions with Individual Nucleotide Resolution
Published on: April 30, 2011
Posttranslational regulation of I-Ed by affinity for CLIP
Cornelia H Rinderknecht1, Michael P Belmares, Tatiana L W Catanzarite
1Program in Immunology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 20, 2007
Summary
Altering the binding affinity between MHC class II molecules and CLIP peptides influences the stability and presentation of antigens. This finding is crucial for understanding autoimmune disease pathogenesis and immune response regulation.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmune Diseases
Background:
- Certain MHC class II alleles associated with autoimmune diseases exhibit low stability with CLIP.
- This low stability suggests a potential role in autoimmune pathogenesis.
- The invariant chain (Ii) and DM molecule are known chaperones in MHC class II peptide loading.
Purpose of the Study:
- To investigate the cellular effects of modifying the affinity between MHC class II and CLIP.
- To understand the role of CLIP affinity in the stability and function of the I-E(d) MHC class II molecule.
- To explore the interplay between invariant chain (Ii) and DM in MHC class II chaperoning.
Main Methods:
- Utilized invariant chain (Ii) mutants with altered CLIP affinity for the mouse I-E(d) MHC class II allele.
- Assessed the abundance, half-life, and cell surface expression of I-E(d).
- Evaluated antigen presentation to T cells in cell lines expressing wild-type or mutant Ii.
Main Results:
- Increased CLIP affinity for I-E(d) led to greater I-E(d) abundance, stability, and cell surface expression.
- Invariant chain (Ii) demonstrates post-endoplasmic reticulum chaperoning of MHC class II via CLIP.
- Effects were less pronounced in DM-expressing cells, indicating complementary roles of Ii and DM.
Conclusions:
- Modulating CLIP affinity influences MHC class II stability and chaperoning by the invariant chain (Ii).
- The impact of CLIP affinity variation on immune responses is greatest in cells with limited DM activity.
- Increased CLIP affinity may restrict peptide loading to DM-containing compartments, ensuring proper antigen editing.
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