HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 (Cluster of Differentiation 74), is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the CD74 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II

MHC class II

MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....

 protein. The cell surface form of the invariant chain is known as CD74.

Function

The nascent MHC

Major histocompatibility complex

Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...

 class II protein in the rough ER

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 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. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome

Endosome

In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...

 containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S

Cathepsin S

Cathepsin S, also known as CTSS, is a protein which in humans is encoded by the CTSS gene.The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine protease that may participate in the degradation of antigenic proteins to peptides for presentation on MHC class...

 (cathepsin L

Cathepsin L

Cathepsin L can refer to:* Cathepsin L1, previously called cathepsin L* Cathepsin L2 or cathepsin V...

 in cortical thymic epitheial cells), leaving only a small fragment called 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 blocks peptide binding until 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...

 binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.

Possible interactions

In limited cases, CD74 might interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Macrophage migration inhibitory factor

Macrophage migration inhibitory factor

Macrophage migration inhibitory factor also known as glycosylation-inhibiting factor , L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene.- Structure :...

.

External links

• Overview at Davidson College
  Davidson College
  Davidson College is a private liberal arts college in Davidson, North Carolina. The college has graduated 23 Rhodes Scholars and is consistently ranked in the top ten liberal arts colleges in the country by U.S. News and World Report magazine, although it has recently dropped to 11th in U.S. News...
  
  (student generated)
• School of Crystallography The Invariant Chain