The MHC and MHC molecules 1

Published on May 8, 2022   42 min

Other Talks in the Series: The Immune System - key concepts and questions

Hello. This is Jim Kaufman from the University of Edinburgh and the University of Cambridge, with the first of two talks on the MHC and MHC molecules.
We're going to cover a variety of topics in these two talks. But we're going to begin this first talk with the definition and the central role of MHC molecules.
First, what is the MHC? It stands for the major histocompatibility complex. It was discovered first in mice as a histocompatibility two, or H-2, locus and then in humans as HLA, or Human Leukocyte Antigen. These two genetic loci were the loci that were most responsible for rapid graft rejection. That's reflected in the name. It's the major complex or region that's responsible for the compatibility of tissues, which is what 'histo' means. We now know that both of these regions are really large and they determine the "transplantation antigens" for which there are thousands of genetic variants, which geneticists call "alleles". These are the molecules or genes that are matched by "tissue typing" for transplants in order to avoid rejection by the immune system. H-2 and HLA are the best characterized mammalian MHCs, due to their importance in biomedicine.
It was a big puzzle for many years as to why this complicated system evolved. It has many thousands of MHC alleles and involves robust immune responses and it seemed ridiculous that it existed just to frustrate transplant surgeons. Now we know that MHC molecules are used by the immune system to detect infections inside cells, cancers and threats outside of cells. The high polymorphism, that is the large number of alleles, is (mostly) driven by a molecular arms race with pathogens.