Intracellular antibody-mediated degradation (IAMD) is a neutralization mechanism of intracellular

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

-mediated immunity whereby an effector protein,

TRIM21 Tripartite motif-containing protein 21, also known as E3 ubiquitin-protein ligase TRIM21, is a protein that in humans is encoded by the ''TRIM21'' gene. Alternatively spliced transcript variants for this gene have been described but the full-length ...

, directs antibody bound

virions A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

to the

proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...

where they are degraded. As yet, it has only been observed to act against the

adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...

but is likely to also be effective against other non-enveloped viruses.

Mechanism of action

In IAMD, the neutralization of the pathogen follows a non-cytotoxic mechanism. That is, the infected cell is not attacked as in

Antibody-dependent cell-mediated cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose ...

, instead the virions are rapidly destroyed and the cell may be relieved of infection. #

Immunoglobulin G Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

(IgG) binds specifically to the target antigen presented on the pathogen extracellularly #The antibody bound pathogen infects a host cell #In the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

, TRIM21 (a protein of the

Tripartite motif family The tripartite motif family (TRIM) is a protein family. Function Many TRIM proteins are induced by interferons, which are important component of resistance to pathogens and several TRIM proteins are known to be required for the restriction of infe ...

) binds with high affinity to IgG #TRIM21 is conjugated with

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

, which directs the complex to the proteasome #Degradation by

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

of both the protein capsid and the antibody occurs, but not the TRIM21 protein

Resistance to mutants

There are a number of reasons why IAMD is so resistant to evasion by mutants through evolution: *The targeting of pathogens by antibodies is adaptive while the degradation is innate; the overall response therefore combines both

adaptive Adaptation, in biology, is the process or trait by which organisms or population better match their environment Adaptation may also refer to: Arts * Adaptation (arts), a transfer of a work of art from one medium to another ** Film adaptation, a ...

and

innate immunity The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

. *The proteasomal targeting is mediated by the autoubiquitination of TRIM21, there is no direct interaction with the pathogen so mutants which evade ubiquitination themselves cannot evade IAMD. *Unlike extracellular humoral immune responses, this intracellular mechanism is expressed in most human tissues and is an example of encapsulating immunity as opposed to mere immune surveillance.

References

{{Clear Immune system

Mechanism of action

Resistance to mutants

See also

References