Exploring Novel Immunoglobulin Manipulation Activities – ENIgMA
Antibodies are essential biotechnological tools, owing to their ability to tightly and specifically bind to a given antigen. Several strategies used to manipulate immunoglobulins have been developed by using microbial effectors normally involved in immune evasion. In 2016, Partner 1 has identified a novel and atypical mycoplasma virulence system that can bind and cleave immunoglobulins, Mycoplasma Immunoglobulin Binding protein and the Mycoplasma Immunoglobulin Protease (MIB and MIP, respectively).
Recently, Partner 1 and Partner 2 have solved the structure of the tripartite complex comprised of MIB, MIP and the Fab fragment of an IgG, and revealed that MIB actively promotes the dissociation of pre-established antigen-antibody complexes, resulting in completely free antigens.
This feature is unique and is the first report on a generic and native mechanism of antigen separation from antibodies. Given its properties, we propose that the MIB-MIP system should be further studied, as it has the potential to be converted into a set of new, efficient biotechnological tools. The ENIgMa project is therefore aimed at the Exploration of these Novel Immunoglobulin Manipulation Activities, to gather the knowledge that will pave the way towards the development of these tools. In this framework, we are asking 3 main questions:
i. What are the molecular determinants of the MIB-immunoglobulin interactions?
ii. What is the mechanism of immune complex dissociation by MIB?
iii. How is MIB “reset” to its unbound state?
These questions will be addressed in Work Package 1-3, and the knowledge gathered in this project will be applied to the development of prototype tools in a Work Package 4.
Project coordination
Yonathan ARFI (Biologie du Fruit et Pathologie)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
IP-HI IP-Laboratoire Immunologie Humorale
MFP MICROBIOLOGIE FONDAMENTALE ET PATHOGÉNICITÉ
BFP Biologie du Fruit et Pathologie
Help of the ANR 623,743 euros
Beginning and duration of the scientific project:
January 2022
- 48 Months