Antibody structure and function: antibody structure

Hi, my name is Dr. Mike Clark, and I was formerly Reader in Therapeutic Molecular Immunology at the Department of Pathology, Cambridge University. This lecture is going to be about antibody structure and function and is going to be divided into two parts. In part 1 of the lecture, I'm going to deal with the structures.

Immunology presents us with a real problem, and that is that we don't know in advance what infectious diseases we will encounter during our lifetime. We're going to be faced with a vast array of different pathogens that will infect us at different times during our life. Each of those different pathogens will present us with an array of different antigens that they express, and we will have to make an immune response that deals with all those different antigens. This is the problem of the generation of diversity in the formation of antibodies. We need to have antibodies that are specific to all the different antigens that we might encounter during our lifetime. In this lecture, we're going to, first of all, deal with the basic antibody structure. This is the structure of the standard antibody, its variable regions that bind to these different antigens, and then the constant regions. Then we'll go on to deal with the structure of different classes and subclasses of antibody that will mediate the different functions that we will deal with in the next lecture.

What we have here is the schematic of an IgG structure, and I think many of you will be familiar with this. It's a basic Y-shaped molecule that is depicted in many publications. This is really the basic structure of the IgG molecule as I show here, the one that's most commonly discussed. What you can see is that the molecule has effectively a certain symmetry about it. It's actually a pseudo-axis of rotational symmetry about the vertical axis in this picture. What you can see is we've got an antigen-binding site indicated on the top right here, and there are actually two antigen-binding sites in this molecule: one on the left and one on the right. We've got various domains, these are protein domains that make up the entire structure. Each of these is delineated by those ellipses on the screen. The molecule is made up of two heavy chains and two light chains. These have got domains which are given letters and numbers. We can see here that we've got domains on the heavy chain, 'H' for heavy chain, which are labeled in this diagram: VH, CH1, CH2, and CH3. These stand for the variable domain of the heavy chain: the first constant domain of the heavy chain, the second constant domain of the heavy chain, and the third constant domain of the heavy chain. Then we've got two other domains up here which are from the light chain. We've got the variable domain of the light chain and the constant domain of the light chain. These are like beads on a string in terms of the protein structure, and the molecule is built up from repeated domains within the structure. Between the heavy chain 1 and the heavy chain 2 domains, there is actually, in this particular molecule, the IgG, there is a more flexible region which is called the hinge. This is, rather the domain, is a more flexible long protein chain that joins the two domains together. Then finally, an indicator on this diagram we've got a glycosylation site, which is commonly conserved in the CH2 region of the IgG molecule. So that's the basic structure and you'll come across this representation over and over again when you look at it, and we'll be referring back to these types of diagrams as we go on with the discussion. It's worth thinking about this in terms of, as I pointed out, you've got a certain repeated structure within it and repeating domains building up the entire subject. Also, you've got the rotational symmetry within this molecule, that the two halves of the molecule; if you rotate the right-hand side and rotate it over to the left, essentially, you've got identical heavy and light chains on each side of this molecule but rotated through a 180 degrees.