Probably sooner or later you think I might start talking to you about T cells. But before I do that, I have to give you an introduction to the major histocompatibility complex. That is the set of genes that produces the set of proteins that will make the activation of T cells possible. So, what we're looking at now is a set of proteins that are very important in activating T cells, you may have heard of them in a different compound text, that is, this is the tissue typing problem that people have when they want to accept a transplant, because the same proteins, here is one of them, that are used to present to TH cells also may trigger the rejection of a kidney or worse. So, what we're going to look at, first of all, it's like where they come from, and then what they look like, and eventually how they're used. So, if we look at this stuff, we find that the proteins that we're looking at, which I've shown here in models, are coded for by a set of closely linked genes found on chromosome 6 in human beings. So, you have this little tricolors as stripe here, because on chromosome 6, on the P or shorter arm, roughly halfway between the centromere, which is here, and the end of it, the telomere here, is a closely linked set of genes. So, the blue parts here are the ones that are going to code for MHC II, the pink ones in the middle will code for the MHC III complex, and the ones on the end are going to code for MHC I. So, what am I talking about? Well, what will happen is everybody will get three of these genes from mum, and three of these genes from dad. So, for the MHC I, here we have the protein that will be produced from the gene. As it turns out, this part of the protein is coded for by the gene, this part of the protein here is coded for by an entirely different gene, that's your- and you have in this location three from mum and three from dad. So, you have six different versions of this one which is going to be used to activate TC cells. As an aside, these are things that can turn traitor on you and kill off your own cells, if you have an autoimmune response, but on the other hand these cells, the T cells, will use these to identify, for example cancer cells or viral infected cells, in order to get rid of them. When they do that, what they will do is recognize a little piece of antigen that will be held on the end of the molecule. So, here I'm going to use this. I'm going to put it here, just to remind you what this is for. I have a somewhat different model of this it's in 3-dimensions that we'll look at again later. So, here's the antigen on my cardboard version, just tends to fall over, and here is the antigen on my 3-dimensional model. So, if you look at this 3-dimensional model, you can see here is the MHC I protein, here is a beta microglobulin that associates with it and here looking in this direction here, is the antigen that's being held to it and you can see it bows out slightly. So, this is the MHC I, and this MHC I is coded for by this region of the gene, the MHC II actually functions as two separate peptides, and here is an example of this. In this case, we will see that the antigen kind of flops over, something we'll look at again, and it's just sort of held on like that. So, here I have two different MHC molecules, this one is I and this one is II. In terms of physical models this was the I and, I should put an antigen on this, this is the II. Notice that in this one I have two separate peptides. So, that when I go into looking at my genes, I will see that when I look at the class II genes am going to see one for the alpha subunit, one for the beta subunit and they're going to come together at the top and my antigen will be held in a groove at the top, flopping over. So, just to orientation. Now, why is this a big deal? Well, it turns out that most of the time this part of the gene here, because it's not very long, will not have any crossing overs in it. So, in other words, this region here is usually inherited as a block and that block is called a haplo type, what's going on here, this kind of terminology usually confuses people. So, let's go look at these genes, while it turns out you only have say three of these genes from mom, for this part, and three from dad. If I look at a whole classroom of you, the chances are, unless I've got related kids in there, everybody will have a different set of just these genes. That's not even going into the IIs which are even more varied. So, there are hundreds of different versions of genes that can code for this protein. Now, you can only get three for mom and three from dad, so you personally only have six of these, but the person sitting next to you probably also has three entirely different versions of these that, again, will have six of them, but then each one of them will be different because there's such an enormous variety of these in the whole wide world. Can be as many as 100 different alleles. That's why it can be very, very difficult to find a bone marrow donor, because, let's face it, if you need a bone marrow transplant, you have to have a perfect match for all of those alleles and all of the ones that make II. Otherwise, that bone marrow will attack you and you will die. So, in situations where you need a transplant of this nature, the best place to go to, if you don't have an identical twin, and most of us don't, is a full sibling.
