So, with these experiments, and others ones additionally to them, we began to get a better picture of what an antibody was all about. Here, is my model that shows you a lot of the details of an antibodies function and how its structure interacts with antigen. Having said that, I would like to say that this is a good model for showing somethings and there are plenty of other models that will also illustrate many of the properties of the antibody. This one is a really good one for analyzing how the structures fit together. If you want to see what it really looks like, you need a space-filling molecule, and those models tend to be a lot harder to interpret. So, let's just take a look at this model carefully, and see what we can learn about antibodies generally before we start looking into the specifics of how you put together the chains, and how that affects the various functions. So, first of all, what we've got in this antibody is, the light chain is here, in light blue and hot pink. Here on the other side, it turns out in any antibody these two will be identical. So, let's mark this light chain. Here we come into, again, one of those peculiarities of the terminology that you have in immunology. A lot of times a peptide is called a chain. I never heard of that usage in any other context, but the word chain simply means peptide. So, if I have an antibody here, what I have is a quaternary association of four peptides, two light chains, and two heavy. So in this model, the heavy chain starts here, comes down through, and then here is the part of the heavy chain in this stem. So, that in this case, the Fc region that we isolated before is this region here, the bottom part. The Fab fragments will be the whole light arm. So, I would get one Fab fragment here, and one Fab fragment here, and again a Fab two fragment would be from here up, and this part would be the Fc fragment from here down depending on where you clipped it exactly. Now, if you look at this, you can see that the light chain is made up of two immunoglobulin domains. One that I've done in light blue and one that I've done in pink. This particular heavy chain is made up of one, two, three, four immunoglobulin domains, and a bendy region in between. This is a hinge region that can flop around. In other antibodies, there will be another, we'll see, immunoglobulin domain here and it'll be more rigid. Now, in both of these, I have done sections of the antibodies in blue and dark blue, but I've done this part of the antibodies whether they're the heavy part chain, or the light chain, I've done in pink and yellow with a little touch of green. So, why did I do that? This part in here, the pink yellow parts with the green are the variable domains and the loops that stick out here one, two, three, one, two, three will be loops that contact the antigen. So, this part of the antibody here is more or less constant from antibody to antibody. There are some differences, the differences are not trivial, but in general, these don't change. Whereas, when I look at this part of the antibody, I find its variable in truth. This part from here to here is not all that variable. What's going to be really variable are the loop regions in here. But, let's take another backup look here. We can see the immunoglobulin domains because we can see the bread and butter sandwich. I'm hoping you can catch that. I will put another picture of this in your notes in detail. So look at it, you can see that I have used these cute sequence to designate the disulfide linkages and then, somewhere in here forcing these two heavy domains apart in the Fc, I have some white fuzzy stuff. This stands for the two oligosaccharides that are attached to the second domain from the end. This is a smallish carbohydrate. It is hooked on here and it helps to pull apart this part of the Fc stem. It's going to be very important in signaling to other parts of the immune system just how to treat whatever this antibody is hooked up against. So, we've got again, here's our light chain molecular weight about 50,000. Here is the heavy chain, molecular weight about 100,000. Here are the sequence indicating disulfide bonds. Some of them are part of the bread and butter sandwich domains that hold this together. Others here, here, here are holding together the light and heavy chains, and the two heavy chains together. So, that's stabilizing this and again we have a carbohydrate as part of the Fc stage. So, this will give you an overview of what the antibodies different parts are and how they relate. We're going to look at just how you make these funny color regions when we look at gene rearrangement, but we can hold that for now. What I want to do now is take a closer look at just this light chain and that's part D. So, before we go into the classes, I want to take a closer look at the light chain or peptide. If you recall that is on this part of the antibody. If I take this and actually redraw it again, I can see that what I've got is a peptide that is folded into an immunoglobulin domain. This is the constant part of the peptides, so this would be the immunoglobulin domain here. After that, it takes a bend and it goes into the variable domain. The variable domain of the light chain is going to be divided into a joining and a variable region. It's actually going to have nine of these things. Now, this will be the N terminal of the peptide. This is where the peptide synthesis begins, translation begins here, continues through here into this yellow-orange region, and then into the constant region, and this will be the N terminal here. So, that on this model, here's the N terminal, here's the stabilizing disulfides, here is the junction to the joining region, and into the constant. Both of these are immunoglobulin domains with the characteristics that we discussed before. This region, the constant domain, will have disulfide bonds that help join it to the heavy chain. The variable region is really something that is just basically there to display the three loops that we see here, here, and here. Because these are the loops that will be involved in binding to the antigen. So, here is the light chain drawn out and here it is on the model. Now, this one then has the properties here of the antibody recognition region and here we have the constant region. But, it turns out there are actually two kinds of these guys, that you have two different genes. You make a kappa version or you make a lambda version. So, that this part, the whole thing actually can be either kappa or lambda. So, that you've got two different choices of kinds of light chains you can have and even more interesting if you go into humans, they're going to have four different constant variation regions that they can put into the lambda, when they're making the lambda gene ready to roll. So, I have a light chain here that actually comes in a variety of different flavors. I haven't seen any really good explanation for any functional difference between them, but this is one thing you need to remember. Any one cell is going to make either what the kappa or one kind of the lambda. So, that when I have an antibody either both going to be kappa or they're both going to be lambda. The other thing that you need to know is we're about to look at five different classes or types of antibodies. That's going to be based on the specifics of the heavy chain. Any heavy chain can be associated with any light chain. Having said that, in any one cell, a cell is going to pick a type of heavy chain to make and it will pick a type of light chain to make. When they get together, you will have this complex recognition surface and that's what will allow this antibody to specifically identify very specific proteins, especially those that are pathogenic and that's what allows this thing to help you recover from illness.
