More on MHCs

Q. I have a question on MHC receptors being polymorphic, you used the ice cream example about all of us have “different flavors”… but does that mean your MHC receptors are all the same, but just different from all of mine, which are the same as each other ? Or are all MHC receptors polymorphic?

A. That’s a great question! The short answer is: there are many different kinds of MHC receptors, and we each have a mixture of a bunch of different types. It’s not like all of my MHC I receptors are identical, and all of yours are identical. I’ll try to explain a bit more.

Each locus within the MHC I region (A, B, and C) codes for everything you need to make an MHC I receptor. So, for the MHC I receptor, since you have two A loci, two B loci, and two C loci, that means you have the capability to make 6 very slightly different kinds of MHC I receptors (that’s assuming that you don’t have any “repeats” – that is, your As are different from each other, and so are your Bs and your Cs). Check out this diagram from Wikipedia – it shows the different MHC I and II receptors present on a cell:

MHC

These MHC I receptors vary just a tiny bit in their antigen binding domain, so each one has a slightly different ability to bind any given antigen. This is good. You want to have a lot of variability so that you’re prepared for any potential antigen that comes your way.

Same thing goes for the MHC II receptor. There are three gene loci (DP, DQ, and DR), and usually you’ll inherit two different HLA-DP alleles, two different HLA-DQ alleles and two different HLA-DR alleles (sometimes you’ll inherit an additional HLA-DR allele or two just for the heck of it). That means you have the ability to make six (or maybe up to 8) slightly different MHC II receptors.

The weird thing about the expression of these genes is that you express all of them. So instead of just picking one of your HLA-A genes and transcribing that one, you always transcribe both of HLA-As (as well as both of your HLA-Bs and Cs). SO: every cell that expresses MHC I receptors will have 6 different MHC I receptors on its surface, and every cell that expresses MHC II receptors will have at least 6 different MHC II receptors on its surface.


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