Published on March 9, 2022   44 min

Other Talks in the Series: The Immune System - key concepts and questions

Welcome to this talk on chemokines. My name is Dr. James Pease. I'm a reader in leukocyte biology at the National Heart & Lung Institute at Imperial College London, United Kingdom.
The outline of this talk on chemokines is in three parts. In the first part, I'm going to talk about chemokines themselves. I'm going to introduce their classification, their function and their signalling. In the second part, I'll talk about how microbes have corrupted the chemokines system for their own purposes. In the third and final part, I'll talk about work on the therapeutic blockade of chemokine receptors in various diseases. Let's start off by introducing chemokines and talking about their classification, function and signalling.
The term chemokine is a portmanteau. It comes from the phrase chemotactic cytokines and defines cytokines that drive the chemotaxis of cells. That's principally leukocyte migration. Chemokines are small soluble proteins, typically around 8-10 kDa in molecular weight and they adopt a tertiary structure, as shown here in this slide. It's notable for the presence of a 'greek-key' motif, which is three anti-parallel β pleated sheets and the C-terminal α helix. The structure of a chemokine is underpinned by two disulfide bonds, and they're typically secreted as mature peptides following the removal or excision of a short signal peptide.
The family of 40 or so chemokines in the human can be conveniently subdivided into four major classes, and that's based on their arrangement of N-terminal cysteine residues. The majority of chemokines fall into the families known as the CC and the CXC families. CC chemokines concern an N-terminus with two adjacent cysteine residues, whereas the CXC chemokines have a single amino acid interspersed between the cysteines. There are also a couple of minor chemokine families. The CX_3C family contains three amino acids between these N-terminal cysteines. Whilst the C chemokines have a single cysteine residue in their N-terminus. Chemokines are predominately quite basic molecules, and they have several conserved lysine and arginine residues, notably in the C-terminus. The primary function of chemokines is shown on this slide here. They drive the chemotaxis of cells. That can be defined as the directional migration of a cell towards a chemical stimulus.