Major Histocompatibility Complex (MHC) – Antigen Processing and Presentation

by Peter Delves, PhD

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    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.

    About the Lecture

    The lecture Major Histocompatibility Complex (MHC) – Antigen Processing and Presentation by Peter Delves, PhD is from the course Adaptive Immune System. It contains the following chapters:

    • The Major Histocompatibility Complex
    • The MHC Gene Locus

    Included Quiz Questions

    1. HLA-DR
    2. HLA-A
    3. HLA-B
    4. HLA-C
    5. Factor B
    1. MHC I: Present on all nucleated cells in the body MHC II: Present on antigen-presenting cells
    2. MHC I: Alerts CD4+ T cells MHC II: Alerts CD8+ T cells
    3. MHC I: Present on red blood cells MHC II: Present on antigen-presenting cells
    4. MHC I: Binds peptides derived from extracellular antigens MHC II: Binds peptides derived from intracellular antigens
    5. MHC I: Alerts helper T cells MHC II: Alerts cytotoxic T cells
    1. Complement component 3
    2. Factor B
    3. Lymphotoxin
    4. Complement component 4
    5. Tumour necrosis factors-alpha

    Author of lecture Major Histocompatibility Complex (MHC) – Antigen Processing and Presentation

     Peter Delves, PhD

    Peter Delves, PhD

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