Diversity of Major Histocompatibility Complex – Antigen Processing and Presentation

00:01 I’ve already mentioned that the MHC is by far the most diverse set of genes in the human genome.

00:08 So let’s take a few moments to explore this diversity.

00:14 As you can see on this diagram, at the top you can see a bar that is labeled M.

00:21 This is meant to represent the chromosome 6, which is where the MHC in human is that you’ve inherited from your mom.

00:29 So M for maternal chromosome.

00:32 And you can see that there are the HLA Class I genes - HLA-A, B and C, and the MHC Class II genes - HLA-DP, DQ, DR.

00:44 And these genes, as we’ve already heard vary enormously from one individual to another.

00:49 So you might be HLA-A1 or A2 or A3 or A4 and so forth.

00:55 And you can see that this particular individual is HLA-A84.

01:01 So that gene will be transcribed and the HLA-A84 molecule will be put on the surface of that cell.

01:12 This individual has also inherited HLA-B8 variant; could have had B3, B27, B64, whatever from the mother, but in this case the mother’s gene that it’s inherited… this individual has inherited is B8.

01:30 So it puts B8 on its surface.

01:32 And likewise, on the maternal chromosome the variant of HLA-C is HLA-C17.

01:42 Of course there are two chromosomes, one from the father and one from the mother.

01:47 So at the bottom we have the paternal chromosome, from the father.

01:52 And this individual has inherited from their father HLA-A2, HLA-B27; so they do have B27 but it’s come from the father rather than the mother, and HLA-C46.

02:06 So those three molecules are put on the surface.

02:09 So for each HLA type, A or B or C, we potentially have two different variants.

02:19 Now it may be that sometimes, an individual is homozygous for a particular variant.

02:26 So you may have inherited both HLA-A2 from your mom and HLA-A2 from your dad.

02:34 So rather than having six different versions, you may only have five.

02:39 Turning now to the MHC Class II which remember is only expressed on professional antigen presenting cells, you can see the various genes that have been inherited here on the maternal chromosome - DP24, DQ91, DR4; on the paternal chromosome - DP6, DQ69 and DR4.

03:03 And these will additionally be put onto the surface of professional antigen presenting cells.

03:09 Looking now at the centre of that diagram, you can see some numbers that relate to the number of allelic variants.

03:18 And these are approximations based upon sequencing that’s been carried out worldwide of the number of different possibilities.

03:26 So we’ve already mentioned HLA-A1, A2, A3, A4 and so forth.

03:31 If you look at the right hand side of this figure, you’ll see a number underneath HLA-A of greater than 6,000 for the HLA α- chain, HLA Class I α-chain.

03:47 So there are a huge number of different variants that can exist.

03:52 Now you’ll also see for the HLA β- chain for Class I, the number is just one.

03:59 And that is because the HLA β-chain of MHC Class I is not polymorphic, it doesn’t vary.

04:07 It’s only the α-chain that varies.

04:10 Turning now to MHC Class II and those other numbers you can see next to α-chain and β-chain in the middle of the diagram, you can see that both the α-chain and the β-chain vary.

04:21 The β-chain for the DR is very variable whereas the α-chain for the DR, there are actually very few variants that have been described.

04:31 But you can see that there is collectively a huge variability in the MHC genes.