Come Inside

Editor's choice in immunology

By | March 1, 2011


The paper

D.L. Mallery et al., “Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21),” PNAS, 107:19985-90, 2010. Free F1000 Evaluation

The finding

Antibodies work by activating the complement cascade, preventing invading microorganisms from entering cells, or binding to a pathogen and marking it for destruction by immune cells. Now, Leo James and colleagues at the MRC-LMB in Cambridge have discovered a fourth method that works inside cells, providing a “last line of defense” against infection.

The ambush

James’ lab observed that antibodies can remain bound to adenovirus as it infects cells. The result sparked their curiosity, because they had previously shown that the intracellular protein TRIM21 binds to the Fc region of antibodies with higher affinity than any other antibody receptor in the body.

They found that TRIM21 adds ubiquitin to the adenovirus-antibody complex, targeting it for destruction by the proteasome. The finding “adds conceptually to the immune response,” says F1000 Member David Alpers.

The patents

TRIM21 only works if the virus doesn’t shed the antibody as it enters the cell. This means it should be effective against all nonenveloped viruses, such as rotaviruses and noroviruses, which cause diarrhea and gastroenteritis. James’ lab is in the process of cataloging which infections retain antibodies, and looking for other TRIM21-like proteins. They are also trying to develop novel antiviral therapies, having already applied for patents covering the use of synthetic TRIM21 to treat infections.

F1000 evaluators: L. Walter (German Primate Center) D. Alpers (WUSM)N. Vigneron & B. Van den Eynde (Ludwig Inst for Cancer Res) G. Versteeg & A. Garcia-Sastre (Mount Sinai Sch of Med)D. Koch & N. Sawtell (Cincinnati Children’s Hosp Med Cen)

Add a Comment

Avatar of: You



Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Popular Now

  1. Major German Universities Cancel Elsevier Contracts
  2. Running on Empty
    Features Running on Empty

    Regularly taking breaks from eating—for hours or days—can trigger changes both expected, such as in metabolic dynamics and inflammation, and surprising, as in immune system function and cancer progression.

  3. Most of Human Genome Nonfunctional: Study
  4. Identifying Predatory Publishers