MHC Class II molecules are found only on a few specialized cell types, including macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s, dendritic cell

Dendritic cell

Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s and B cells, all of which are professional antigen-presenting cells (APCs).

The peptides presented by class II molecules are derived from extracellular proteins (not cytosolic as in class I

MHC class I

MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

); hence, the MHC class II-dependent pathway of antigen presentation is called the endocytic or exogenous pathway.

Loading of class II molecules must still occur inside the cell; extracellular proteins are endocytosed

Endocytosis

Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

, digested in lysosome

Lysosome

thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...

s, and bound by the class II MHC molecule prior to the molecule's migration to the plasma membrane.

Structure

Like MHC class I

MHC class I

MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

 molecules, class II molecules are also heterodimers, but in this case consist of two homologous peptides, an α and β chain, both of which are encoded in the MHC. The subdesignation α1, α2, etc refers to separate domains within the HLA gene; each domain is usually encoded by a different exon within the gene, and some genes have further domains that encode leader sequences, transmembrane sequences, etc.

Because the antigen-binding groove of MHC class II molecules is open at both ends while the corresponding groove on class I molecules is closed at each end, the antigens presented by MHC class II molecules are longer, generally between 15 and 24 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 residues long.

Reaction to bacteria

Because class II MHC is loaded with extracellular proteins, it is mainly concerned with presentation of extracellular pathogens (for example, bacteria that might be infecting a wound or the blood). Class II molecules interact exclusively with CD4

CD4

CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

⁺ ("helper") T cells (T_H2). The helper T cells

T helper cell

T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...

 then help to trigger an appropriate immune response which may include localized inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 and swelling due to recruitment of phagocytes or may lead to a full-force antibody immune response due to activation of B cell

B cell

B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s.

Synthesis

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

CLIP (protein)

CLIP or Class II-associated invariant chain peptide is the part of the invariant chain that binds MHC class II groove and remains there until the MHC receptor is fully assembled...

 which
maintains blockage of the peptide binding cleft on the MHC molecule. An MHC class II-like structure, HLA-DM

HLA-DM

HLA-DM is an intracellular protein involved in peptide presentation by MHC class II. It is encoded by the genes and .In the endosomes, HLA-DM functions by promoting the dissociation of the CLIP peptide from MHC class II which allows endosomal peptides to bind...

, facilitates CLIP

CLIP (protein)

CLIP or Class II-associated invariant chain peptide is the part of the invariant chain that binds MHC class II groove and remains there until the MHC receptor is fully assembled...

 removal and allows the binding of peptides with higher affinities. The stable class II MHC is then presented on the cell surface.

Genes

Alpha

Beta >- | HLA-DM HLA-DM HLA-DM is an intracellular protein involved in peptide presentation by MHC class II. It is encoded by the genes and .In the endosomes, HLA-DM functions by promoting the dissociation of the CLIP peptide from MHC class II which allows endosomal peptides to bind...

HLA-DMA HLA-DMA HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.-Further reading:...

HLA-DMB HLA-DMB HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.-Further reading:... >- | HLA-DO HLA-DO HLA-DO is a dimeric protein composed of α- and β-subunits which assists in the down-regulation of HLA-DM....

HLA-DOA HLA-DOA HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.-Further reading:...

HLA-DOB HLA-DOB HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.-Further reading:... >- | HLA-DP HLA-DP HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that is composed of 2 subunits, DPα and DPβ. DPα and DPβ are encoded by two loci, HLA-DPA1 and HLA-DPB1, that are found in the MHC Class II region in the Human Leukocyte Antigen complex on human chromosome 6 .Less...

HLA-DPA1

HLA-DPB1 HLA-DPB1 HLA class II histocompatibility antigen, DP beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.-Further reading:... >- | HLA-DQ HLA-DQ HLA-DQ is a cell surface receptor type protein found on antigen presenting cells. DQ is an αβ heterodimer of the MHC Class II type. The α and β chains are encoded by HLA-DQA1 and HLA-DQB1, respectively. These two loci are adjacent to each other on chromosome 6p21.3. Both the α-chain and β-chain...

HLA-DQA1 HLA-DQA1 Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 and also denotes the genetic locus which contains this gene... , HLA-DQA2 HLA-DQA2 HLA class II histocompatibility antigen, DQ alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system....

HLA-DQB1 HLA-DQB1 Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene... , HLA-DQB2 HLA-DQB2 HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.-Further reading:... >- | HLA-DR

HLA-DRA HLA-DRA HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable...

HLA-DRB1 HLA-DRB1 HLA class II histocompatibility antigen, DRB1-9 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. DRB1 encodes the most prevalent beta subunit of HLA-DR.- Function :... , HLA-DRB3, HLA-DRB4 HLA-DRB4 Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both anchored in the... , HLA-DRB5 HLA-DRB5 HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.- Function :The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha and a beta chain , both...

External links

• http://www.merck.com/mmpe/sec13/ch163/ch163a.html