Proteasome - Role in The Immune System

class="main">

Role in The Immune System

The proteasome plays a straightforward but critical role in the function of the adaptive immune system. Peptide antigens are displayed by the major histocompatibility complex class I (MHC) proteins on the surface of antigen-presenting cells. These peptides are products of proteasomal degradation of proteins originated by the invading pathogen. Although constitutively expressed proteasomes can participate in this process, a specialized complex composed of proteins whose expression is induced by interferon gamma produces peptides of the optimal size and composition for MHC binding. These proteins whose expression increases during the immune response include the 11S regulatory particle, whose main known biological role is regulating the production of MHC ligands, and specialized β subunits called β1i, β2i, and β5i with altered substrate specificity. The complex formed with the specialized β subunits is known as the immunoproteasome. Another β5i variant subunit, β5t, is expressed in the thymus, leading to a thymus-specific "thymoproteasome" whose function is as yet unclear.

The strength of MHC class I ligand binding is dependent on the composition of the ligand C-terminus, as peptides bind by hydrogen bonding and by close contacts with a region called the "B pocket" on the MHC surface. Many MHC class I alleles prefer hydrophobic C-terminal residues, and the immunoproteasome complex is more likely to generate hydrophobic C-termini.

Due to its role in generating the activated form of NF-κB, an anti-apoptotic and pro-inflammatory regulator of cytokine expression, proteasomal activity has been linked to inflammatory and autoimmune diseases. Increased levels of proteasome activity correlate with disease activity and have been implicated in autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis.

The proteasome is also involved in Intracellular antibody-mediated proteolysis of antibody bound virions. In this neutralisation pathway, TRIM21 (a protein of the tripartite motif family) binds with immunoglobulin G to direct the virion to the proteasome where it is degraded.

Read more about this topic:  Proteasome

Famous quotes containing the words role in, immune system, system, role and/or immune:

    Language makes it possible for a child to incorporate his parents’ verbal prohibitions, to make them part of himself....We don’t speak of a conscience yet in the child who is just acquiring language, but we can see very clearly how language plays an indispensable role in the formation of conscience. In fact, the moral achievement of man, the whole complex of factors that go into the organization of conscience is very largely based upon language.
    Selma H. Fraiberg (20th century)

    The moral immune system of this country has been weakened and attacked, and the AIDS virus is the perfect metaphor for it. The malignant neglect of the last twelve years has led to breakdown of our country’s immune system, environmentally, culturally, politically, spiritually and physically.
    Barbra Streisand (b. 1942)

    UG [universal grammar] may be regarded as a characterization of the genetically determined language faculty. One may think of this faculty as a ‘language acquisition device,’ an innate component of the human mind that yields a particular language through interaction with present experience, a device that converts experience into a system of knowledge attained: knowledge of one or another language.
    Noam Chomsky (b. 1928)

    All of the assumptions once made about a parent’s role have been undercut by the specialists. The psychiatric specialists, the psychological specialists, the educational specialists, all have mystified child development. They have fostered the idea that understanding children and promoting their intellectual well-being is too complex for mothers and requires the intervention of experts.
    Elaine Heffner (20th century)

    The moral immune system of this country has been weakened and attacked, and the AIDS virus is the perfect metaphor for it. The malignant neglect of the last twelve years has led to breakdown of our country’s immune system, environmentally, culturally, politically, spiritually and physically.
    Barbra Streisand (b. 1942)