Major Histocompatibility Complex (MHC) – Antigen Processing and Presentation

00:01 The MHC is the major histocompatibility complex.

00:08 It’s called that because it’s a complex of genes, it’s not a single gene.

00:13 And it’s a complex of genes that are the major determinants of tissue compatibility during transplantation.

00:21 That’s how it was first discovered.

00:23 When people were exploring, doing skin grafts for example in mice, between different strains of mice, they recognized that the skin graft from a different strain of mouse would be rejected, immunologically rejected due to recognition of these MHC molecules.

00:40 Well of course, MHC did not evolve to frustrate attempts at transplantation.

00:46 It’s a consequence of the diversity of the MHC but it’s not why we have an MHC.

00:51 We have MHC to show protein antigens in the form of peptides to T-cells.

00:58 In each individual species, the MHC is given a particular name.

01:02 You only need to really know about two of them.

01:05 In the human, it’s called HLA.

01:08 And in the mouse, it’s called H-2.

01:11 It’s worth knowing that because a lot of immunology is worked out in the mouse.

01:15 So when you’re reading textbooks and so forth, you may often come across H-2.

01:19 It’s simply the MHC of the mouse, just like HLA is the MHC of the human.

01:28 There are two classes of MHC - MHC Class I and MHC Class II.

01:36 And they are very similar in structure and very similar in what they do as we’ll learn very shortly.

01:43 There are three types of MHC Class I in the human: HLA-A, HLA-B and HLA-C.

01:52 And for Class II we have HLA-DP, HLA-DQ and HLA-DR.

02:00 The MHC Class I molecules are present on all nucleated cells in the body.

02:05 That’s essentially all cells in the body apart from red blood cells.

02:11 However, the MHC Class II is only present on a very limited number of cell types.

02:17 Essentially professional antigen presenting cells, which are the dendritic cells, the macrophages and the B-cells, and on thymic epithelium.

02:27 And in fact, these professional antigen presenting cells are defined as such by having MHC Class II on their surface. Now I’ve already mentioned that Class I is present on all nucleated cells in the body. And of course dendritic cells, macrophages, B-cells, thymic epithelium, they’re nucleated cells as well. So these cells have both MHC Class I and MHC Class II.

02:50 So it’s not an alternative, it’s an addition to the Class I.

02:54 The function of MHC Class I is to alert CD8+ cytotoxic T-cells to the presence of intracellular antigens; for example, a virus infecting a cell.

03:10 Whereas MHC Class II is specialized to alert CD4+ helper T-cells and CD4+ regulatory T-cells to the presence of extracellular antigens such as bacteria.

03:24 Let’s explore the MHC gene locus.

03:28 We’ve already heard that there are two classes of MHC - MHC Class I and Class II.

03:34 In the humans, these genes are present on chromosome 6.

03:40 HLA Class I consists of HLA-A, -B and -C as we’ve heard.

03:47 And they’re actually arranged in this order.

03:49 You may think that there’s misordering here, looks a bit odd doesn’t it, it’s not ABC, it’s BCA.

03:56 And that’s simply the order that these genes are present on the chromosome.

04:01 And the Class II genes for DQ, DQ, DR.

04:07 In fact there’s another region within the MHC that’s called MHC Class III.

04:12 These genes do not actually encode antigen presenting molecules.

04:16 So they’re really nothing much to do with what we’re talking about at the moment.

04:20 But actually they do encode molecules that are part of the immune response.

04:25 So complement component C4, complement component Factor B that’s part of the alternative pathway of complement activation, complement component C2, lymphotoxin which is a cytokine and another cytokine, TNF-α, are all encoded within the MHC Class III region. But we’re going to focus our attention now on the MHC Class I and Class II antigen presenting molecules.