TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity.

Stian Foss,Inger Sandlie,Leo C James,Ruth Watkinson,Jan Terje Andersen

doi:10.1111/imr.12363

Abstract

Antibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody-mediated protection extends to the cytosolic compartment of cells. This postentry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. Here, we summarize our current understanding of how TRIM21 orchestrates humoral immunity in the cytosolic environment.

Highlights

Antibodies are a crucial part of the immune response toward invading pathogens such as viruses, and the induction of so-called neutralizing antibodies is a primary goal of vaccination [1]
tripartite motif containing 21 (TRIM21) detects antibodies that are carried by pathogens into the cytosol
TRIM21 mediates antibody-dependent cellular neutralization (ADIN), a highly efficient viral elimination mechanism and concomitantly activates proinflammatory signaling resulting in a protective response

Summary

Introduction

Antibodies are a crucial part of the immune response toward invading pathogens such as viruses, and the induction of so-called neutralizing antibodies is a primary goal of vaccination [1]. This article is a part of a series of reviews covering Fc Receptors appearing in Volume 268 of Immunological Reviews. Development of broadly neutralizing antibodies specific for major human pathogens such as human immunodeficiency virus (HIV) and influenza virus [2, 3]. Neutralization of viruses by antibodies is predicted to depend on high-affinity binding to specific epitopes of surface-exposed viral proteins

ADIN is a highly efficient neutralization mechanism

Conclusions and prospects