See also MHC I molecules

Structure: and Divsersity

Class II MHC genes encode two different polypeptide chains, an ? chain and a  ? chain which associate by noncovalent interactions. The peptide binding cleft in class II molecules is open at both ends, allowing longer peptides to extend beyond the ends, like a long hot dog in a bun. Peptides bound to class II MHC molecules maintain a fairly constant elevation on being cleft. 

Calss I and II HLA molecuels exhibit extnsive polymorphisms generated by systematic recombinatorial and point mutation events during cell differentation and maturation resulting form allelic diversity of the parents; as such, hundred of different HLA types exist through the world’s popluation, reuslting in a alrge immunoglogical diversity. Such extensive HLA diversity is the root casue fo tissue or organ tranplant rejection between individuals as well as of differing individual susceptibility and/or resistance to infectious diseases. HLA molecuels also contribute significantly to autoimmunity and cancerl. Weidanz (US 2006/0034850)

Where MHC II molecules are found:

Class II MHC molecuels, designated HLA class II in humans, bind and display peptide antigen ligands upon the cell surface. Unlike class I MHC molecuels which are expressed on virtually all nucleated cells, class II are normally confined to specialized cells, such as B lymphocytes, macropahges, DCs and other APCs which take up foreign antigens form the extracellular fluid via an endocytic pathway. The peptides they bind and present are derived form extracellular foreign antigens, such as products of bacteria that multiply outside the cells, wherein such products include protein toxins secreted by the bacteria that often have deleterious effects. In this manner, class II molecuels convey information regarding the fitness of the extracellular space in the vicinity of the cell displaying the class II molecule to immune efetor cells, including but not limited to CD4+ helpter cells. The extemrination of such patogens is accomplished by both helping B cells making antibodies against microbes as well as toxin produced by such such microbes and by activating macrophages to destroy ingested microbes. Weidanz (US 2006/0034850)

Antigen Processing:

MHC genes encode glycoproteins expressed primarily on antigen presenting cells (,  , thymic epithelia cells and  ). Such glycoproteins present processed antigenic peptides to TH (CD4 + cells). Class II MHC molecules bind peptides derived from exogenous antigens that are internalized by or . Once an antigen is internalized, it is degraded into peptides within compartments of the . Internalized antigen moves from early to late endosomes and finally to lysosomes, encountering lower pH in each compartment.

Since antigen-presenting cells express both class I and II MHC molecules, a mechanism exists to prevent class II MHC molecules which are synthesized within the RER, from binding to the same set of antigenic peptides as the . A special polypeptide, called the invariant chain, ensures this by associating with newly synthesized class II MHC heterodimers in the ER. Part of its polypetide chain lies within the peptide binding groove of the MHC protein, thereby blocking the groove from binding other peptides in the lumen of the ER. 

The invariant chain also directs class II MHC proteins from the trans Golgi network to a late endosomal compartment. Here, the invariant chain is cleaved by proteases, leaving only a short fragment bound in the peptide binding groove of the MHC protein, called  CLIP (class II associated invariant chain peptide). HLA-DM, a nonclassical MHC class II molecule expressed within endosomal compartments, mediates exchange of antigenic peptides for CLIP. 

Monocytes and that have not interacted with antigen express only low levels of class II molecules. Sometimes class II expression is related to the cell’s differentiation stage. For example, class II molecules cannot be detected on preB cells but are expressed on the membrane of mature B cells.