Question

Upregulation of MHC class Il molecules on the surface of antigen-presenting cells occurs during infection. What is this aided by? Select one: a. Destablization of the interaction between the invariant chain and MHCl in the ER O b. Accumulation of HLA-DO in response to inflammatory cytokines c. Deacidification of endocytic vesicles d. IFN-V induced expression of HLA-DM, but not HLA-DO

Answer 1

ANSWER IS OPTION D- IFN-y induced expression of HLA-DM , But not HLA-DO

These molecules are constitutively expressed in professional, immune antigen-presenting cells, but may also be induced on other cells by interferon γ.They are expressed on the epithelial cells in the thymus and on APCs in the periphery. MHC class II expression is closely regulated in APCs by CIITA, which is the MHC class II transactivator. CIITA is solely expressed on professional APCs however, non-professional APCs can also regulate CIITA activity and MHC II expression. As mentioned interferon-y (IFN-y) triggers the expression of CIITA and is also responsible for converting monocytes which are MHC class II negative cells into functional APCs that express MHC class II on their surfaces.

During synthesis of class II MHC in the endoplasmic reticulum, the α and β chains are produced and complexed with a special polypeptide known as the invariant chain. The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway (such as those that would be loaded onto class I MHC).

The invariant chain also facilitates the export of class II MHC from the ER to the golgi, followed by fusion with a late endosome containing endocytosed, degraded proteins. The invariant chain is then broken down in stages by proteases called cathepsins, leaving only a small fragment known as CLIP which maintains blockage of the peptide binding cleft on the MHC molecule. A MHC class II-like structure, HLA-DM, facilitates CLIP removal and allows the binding of peptides with higher affinities. The stable class II MHC is then presented on the cell surface.

DOWNREGULATION OF MHC CLASS II

Antigen loading is modulated by endosomal protein content and the endosomal environment. In B cells, the ability of HLA-DM to interact with MHC class II is regulated by a second MHC-class-II-like protein, HLA-DO. HLA-DO binds to HLA-DM and inhibits it from catalyzing peptide exchange on the MHC class II molecule.Inhibition of HLA-DM activity leads to a concomitant increase in αβ-CLIP complexes in both the intracellular antigen-processing compartments and at the PM, and results in diminished immune responses.