CLIP (protein)

CLIP or Class II-associated invariant chain peptide is the part of the

invariant chain 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 that in humans is encoded by the ''CD74'' gene. The invariant chain (Abbreviated Ii ...

(Ii) that binds to the peptide binding groove of

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...

and remains there until the MHC receptor is fully assembled. CLIP is one of the most prevalent self peptides found in the thymic cortex of most

antigen-presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

. The purpose of CLIP is to prevent the degradation of MHC II dimers before antigenic peptides bind, and to prevent

autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

. During MHC II assembly in the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

, the invariant chain polypeptide complexes with MHC II heterodimers. In a late

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

/early

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

cathepsin S Cathepsin S is a protein that in humans is encoded by the ''CTSS'' gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene. Cathepsin S is a member of the peptidase C1 family of cysteine cathepsins, a lysosom ...

cleaves the invariant chain, leaving CLIP bound to the MHC II complex. In the presence of antigenic peptide fragments,

HLA-DM HLA-DM (human leukocyte antigen DM) is an intracellular protein involved in the mechanism of antigen presentation on antigen presenting cells (APCs) of the immune system. It does this by assisting in peptide loading of major histocompatibility com ...

partially binds to the MHC II peptide binding groove and acts as a catalyst, releasing CLIP and allowing peptides to bind. Antigenic peptides have a high affinity for the MHC II groove, and are readily exchanged for CLIP. This occurs in most cells expressing MHC II–however, in

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

HLA-DO Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunod ...

functions as the accessory protein. Both HLA-DM and HLA-DO interact with each other to act as chaperone proteins and prevent the denaturing of MHC II. MHC II with bound antigen is then transported to the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

for

presentation A presentation conveys information from a speaker to an audience. Presentations are typically demonstrations, introduction, lecture, or speech meant to inform, persuade, inspire, motivate, build goodwill, or present a new idea/product. Presenta ...

. CLIP also can affect the differentiation of

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

. MHC II + CLIP complexes are upregulated on maturing

dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...

, which activate and differentiate T cells into Thelper (T_h) and T_cytotoxic (T_c) cells. Th cells can polarize into Th1 or Th2 effector cells depending on the presence of cytokines. High expression of CLIP favors the release of IL-4 and Th2 cell polarization. CLIP plays an important role in preventing autoimmunity. Since MHC is a polymorphic molecule, mutations that prevent CLIP from binding to MHC II leave the peptide binding groove empty. This could lead to the binding of other self-peptides and destruction of healthy cells.

Autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

juvenile dermatomyositis Juvenile dermatomyositis (JDM) is an idiopathic inflammatory myopathy (IMM) of presumed autoimmune dysfunction resulting in muscle weakness among other complications. It manifests itself in children; it is the pediatric counterpart of dermatomyo ...

, and

Graves disease Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...

are all associated with low CLIP protein levels. {{DEFAULTSORT:Clip (Protein) Immune system