Seminar-On the molecular mechanisms regulating the intracellular trafficking of MHC class II molecules
presents a seminar by:
MHC class II molecules play a key role in the initiation of adaptive immune responses against microbes. Their intracellular trafficking and half-life are tightly regulated to ascertain the efficient and coherent display of self and non-self peptides at the surface of antigen-presenting cells. First, the molecular chaperone invariant chain (CD74) is responsible for bringing MHC class II molecules to endosomes where exogenous antigens are degraded. In humans, CD74 exists in two main isoforms, p33 and p35. The latter has a 16 amino acid cytoplasmic extension that encompasses phosphorylation sites and a di-arginine endoplasmic reticulum retention motif. Results will be presented on the general functions of CD74 and on the specific role of p35. Also, the degradation of MHC class II molecules is controlled by the E3 ubiquitin ligase MARCH1. It now appears that ubiquitination of MHC class II molecules also serves as an important signal for the development of dendritic cells. The properties of DCs in MARCH1-deficient mice will be addressed.
The Department of Microbiology and Immunology
Michael Smith Laboratories