Tuesday, 4 February 2014

Molecule of the month January 2013

This month's molecule isn't in fact a single molecule, but rather a class of molecules referred to as both antibodies and Immunoglobulins, or Ig for short. In fact Ig molecules come in several categories (or classes): IgG, IgA, IgM, IgE and IgD. However, they share some common structural and functional features. The classic structure of an antibody molecule (IgG) is shown on the left and is often considered a Y shape. The top arms of the Y provide two surfaces for interaction with the antigen, or invading material which can be a cell, a virus, a foreign object, as long as it can be "recognised" by the so called Fab region (which stands for Fragment antigen binding). The Fc region (of Fragment crystalline) is part protein and part carbohydrate (or Glycan) and is the part of the molecule (or moiety) that interacts with blood cells called B cells or B lymphocytes. The B refers to the receptor proteins on the cell surface that bind to the Fc region of an antibody when the antibody is engaged with an antigen.

The immune response is triggered when an antibody recognises an invading antigen. The two arms embrace the antigen and the IgG (typically) then has an increased affinity for the B cell surface receptor (right). A series of reactions ensue and the antigen is eliminated. (This will be the topic of a later Blog). The antibody molecule is an excellent example of structure related to function. The arms recognise the antigen and the Fc region recognises the cells that eliminate the antigen: antibody complex.

But, I hear you ask, don't we need an antibody for every invading antigen? Re we born with a set of antibodies that protect us from influenza,E.coli, asbestos fibres, cholera etc? Well, we are born with a "library" or antibodies, but only a few molecules of each and we acquire antibodies from our mother's milk. But we also have a machinery that allows us to generate more antibodies than we originally inherited. This is a complex area of Biology and I will only give you a taster. First of all, when an antibody binds to an antigen and then to a B cell. the B cell (which is an antibody factory) produces lots of that specific antibody (we call this clonal expansion). This is one important part of vaccination (more in the future!). We are also able to mix and match segments of the genes that encode the antigen recognition component of an antibody and add it to the common Fc region. So like the chap on the left, we have one head and body (Fc) and a whole set of different hats (each one having a different appearance and recognising different antigens.

What about IgM, Ig E and IgA. These are more specialised antibodies and they look a little different. IgE looks like IgG, but is responsible for your allergic response, recognising pollen grains and triggering histamine release from Mast Cells. Ig A is two copies of an IgG (a dimer) that is found in mucous, saliva, tears and milk. Finally, IgM is a monster (see right) it is a pentamer of Igs, which forms rosettes of antigens. The fundamental unit is a little like IgG, but it assembles into this five membered ring. It is thought to be responsible for the early stages in the immune response, arriving on the scene before IgG.

So, what a great set of molecules and of course, at Cambridge and Switzerland, Cesar Milstein and Georges Kohler discovered a way of making specific antibodies in the lab in the early 1980s. These monoclonal antibodies have been harnessed recently to attack cancer cells. They are the biggest selling therapeutic molecules in the world today. Ever since Rodney Porter (at Oxford, left) and Gerry Edelman in New York worked out the building plan of antibodies in the late 1960s, these molecules have gone from interesting Biology, to useful lab reagents to exciting new therapeutic agents. I hope this has whetted your appetite to find out more!

1 comment:

  1. I received a correction from one of the UK's experts in immunology at the University of Dundee, Jenny Woof. This is just how Science should be discussed! Thanks, Jenny!

    Hi Dave

    I've been meaning to congratulate you on the blog posts on the UTC Innovation Labs blog. I've really been enjoying reading them. I have to pull you up though on one small thing - its to do with my favourite molecule of course - Immunoglobulins, your molecules of the month back in January 2013. You seem to have mixed up B cell receptors (BCR) with Fc receptors. The BCR is in fact a form of the antibody molecule itself, anchored in the cell membrane via C-terminal extensions and associated with other transmembrane polypeptides. B cells are stimulated to become activated and produce soluble forms of Ig (antibodies) when the BCR are cross-linked by binding to antigen. In contrast, Fc receptors are present on phagocytes and other immune cells and serve to bind to the Fc regions of Igs coated onto foreign material (via their Fab arms binding to antigen). I hope this helps. Look forward to reading more of your insightful posts!

    Best wishes