Fab domain and the Fc domain
The Fab domain and the Fc domain (Fig. 1) are the two evolutionarily conserved structural components of antibodies. The Fab domain has a variable antigen-binding region, which is different in every antibody, whereas the Fc domain is a constant structure that is largely similar in different antibodies. The Fc domain engages with other elements of the immune system, including a family of what are called Fc receptors, found on a range of immune and non-immune cells2. A type of antibody known as IgG engages a subfamily of Fc receptors called the FcγRs. The FcγRs fall into two main classes: activating FcγRs (including the proteins FcγRI, FcγRIIa and FcγRIIIa) and the sole inhibitory FcγR, FcγRIIb. FcγR engagement stimulates or inhibits immune cells, respectively, and the balance of activating to inhibitory engagement determines the responses of cell types that have both activating and inhibitory FcγRs2.
Boosting antibody-mediated antiviral responses
Boosting antibody-mediated antiviral responses. Antibodies consist of Fab domains, which bind to disease-causing agents such as viruses, and an Fc domain, which enlists other defence components. Bournazos et al. engineered an antiviral antibody to have an Fc domain that had an enhanced ability to bind to the receptor protein FcγRIIa. This receptor is found on immune cells such as dendritic cells (which express the defence-boosting proteins CD40, CD80 and CD86). Antibody binding to FcγRIIa triggers signalling that drives dendritic-cell maturation, as indicated by a rise in the expression of CD40, CD80 and CD86. The MHC receptor on dendritic cells can present a viral fragment called an antigen. When the TCR protein of an immune cell called a CD8 T cell recognizes viral antigen, it causes the T cell to kill cells infected with the virus.
Bournazos, S., Corti, D., Virgin, H. W. & Ravetch, J. V. Nature https://doi.org/10.1038/s41586-020-2838-z (2020).
