HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC class II deficiency.

As mentioned interferon γ (IFN γ) 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.

Having MHC class II molecules present proper peptides that are bound stably is essential for overall immune function.

[7] 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 apparatus, 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.

In some cells, antigens bind to recycled MHC class II molecules while they are in the early endosomes, while other cells such as dendritic cells internalize antigens via receptor-mediated endocytosis and create MHC class II molecules plus peptide in the endosomal-lysosomal antigen processing compartment which is independent of the synthesis of new MHC class II complexes.

The pathogen is then broken down in a lysosome and a desired component is then acquired and loaded onto a MHC II molecule.

The only current form of treatment is a bone-marrow transplant however even this does not cure the disease and most patients do not live past age ten.

[18] MHC class II genes and molecules are related to a multitude of different diseases, one of which being Type I diabetes.

Alleles of these genes that affect peptide binding to the MHC class II molecules seem to impact Type I diabetes risk the most.