Thomas Vorup-Jensen will present the work of his research group. Title: “The Structural Immunology of Complement Receptors 3 & 4, and why you can’t live without it”

2018.09.21 | Zitta Glattrup Nygaard

The title of his talk is “The Structural Immunology of Complement Receptors 3 & 4, and why you can’t live without it”

Complement receptors (CR) 3 and 4 belong to the family of beta-2 (CD18) integrins. CR3 and CR4 are often co-expressed in the myeloid subsets of leukocytes, but they are also found in NK cells and activated T and B lymphocytes. The heterodimeric ectodomain undergo considerable conformational change in order to switch the receptor from a structurally bent, ligand-binding in-active state into an extended, ligand-binding active state. CR3 binds the C3d fragment of C3 in a way permitting CR2 also to bind concomitantly. This enables a hand-over of complement-opsonized antigens from the cell surface of CR3-expressing macrophages to the CR2-expressing B lymphocytes, in consequence acting as an antigen presentation mechanism. As a more enigmatic part of their functions, both CR3 and CR4 bind several structurally unrelated proteins, engineered peptides, and glycosaminoglycans. No consensus motif in the proteinaceous ligands has been established. Yet, the experimental evidence clearly suggest that the ligands are primarily, if not entirely, recognized by a single site within the receptors, namely the metal-ion dependent adhesion site (MIDAS). Comparison of some recent identified ligands points to CR3 as inclined to bind positively charged species, while CR4, by contrast, binds strongly negative-charged species, in both cases with the critical involvement of deprotonated, acidic groups as ligands for the Mg2+ ion in the MIDAS. These properties place CR3 and CR4 firmly within the realm of modern molecular medicine in several ways. The expression of CR3 and CR4 in NK cells was recently demonstrated to enable complement-dependent cell cytotoxicity toward antibody-coated cancer cells as part of biological therapy, constituting a significant part of the efficacy of such treatment. With the flexible principles of ligand recognition, it is also possible to propose a response of CR3 and CR4 to existing medicines thereby opening a possibility of drug repurposing to influence the function of these receptors.

Venue
The seminar will be held at 12:00 in the Lille Anatomisk Aud. (1231-424).
The talk is 45 minutes in duration, followed by 15 minutes of discussion.

Sign-up
No sign-up is required for the talk itself. However, it is possible to sign-up for a free sandwich, if you follow this link: https://events.au.dk/BiomedicineSeminarOctober2018

Please note the deadline for sandwich sign-up is Monday the 1^st of October.

The program for the rest of 2018 looks like this:

• Wednesday Nov. 15: Poul Henning Jensen
• Wednesday Dec. 6: Martin Roelsgaard Jakobsen

We are additionally hosting some exciting international guest speakers on 25 October, 25 November, 23 and 27 November. Details will follow soon!

Kind regards

The Biomedicine Seminar Organizing Committee
Mikkel Vendelbo
Line Reinert
Søren Egedal Degn
Martin Kristian Thomsen