Changes

[[Image:MHC T cell Interaction.jpg|thumb|right|200px|Molecules of T lymphocyte recognition - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

[[Image:MHC T cell Interaction.jpg|thumb|right|200px|Molecules of T lymphocyte recognition - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

Only peptide associated with self-MHC will interact with and activate [[T cells]], which cannot be activated by a peptide on a foreign cell.

Only peptide associated with self-MHC will interact with and activate [[T cells]], which cannot be activated by a peptide on a foreign cell.

T cells will react against foreign MHC molecules and this is the basis of graft rejection

T cells will react against foreign MHC molecules and this is the basis of graft rejection

[[Image:Location of Polymorphic Residues 1.jpg|thumb|right|150px|Location of Polymorphic Residues - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

[[Image:Location of Polymorphic Residues 1.jpg|thumb|right|200px|Location of Polymorphic Residues - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

Different individuals have different critical amino acids within the MHC i.e. different amino acids that determine peptide binding. This variation is termed '''MHC polymorphism'''.

*Each polymorphic variant is called an '''allele'''

Both type I and type II MHC molecules are highly polymorphic - the most polymorphic regions of class I are in the alpha 1 and alpha 2 domains. The most polymorphic regions of class II are in the alpha 1 and beta 1 domains.

 

* Different individuals have different critical amino acids within the MHC

Most polymorphisms are point mutations and there are millions of variations in [[Immunoglobulins|antibodies]] and TCRs; however, with MHC there is very limited variation between molecules. Allelic variation within the MHC molecule occurs at the peptide binding site and on the top or sides of the binding cleft. Polymorphisms and polygenism in the MHC provides protection from pathogens evading the immune system.

** I.e. different amino acids that determine peptide binding

** This variation is termed '''MHC polymorphism'''

**Each polymorphic variant is called an '''allele'''

*Both type I and type II MHC molecules are highly polymorphic

**Most polymorphic regions of class I are in the alpha 1 and alpha 2 domains

**Most polymorphic regions of class II are in the alpha 1 and beta 1 domains

*Most polymorphisms are point mutations

* There are millions of variations in [[Immunoglobulins|antibodies]] and TCR

** However, with MHC there is very limited variation between molecules

*Allelic variation within the MHC molecule occurs at the peptide binding site and on the top or sides of the binding cleft

*Polymorphisms and polygenism in the MHC protects the population from pathogens evading the immune system

* MHC polymorphism has been best studied in the human

* MHC polymorphism has been best studied in the human

[[Image:Location of Polymorphic Residues 2.jpg|thumb|right|150px|Location of Polymorphic Residues - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

[[Image:Location of Polymorphic Residues 2.jpg|thumb|right|200px|Location of Polymorphic Residues - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

 

The variation within MHC class I is entirely based on the class I heavy chain (the β2m is invariant). The variation within MHC class II is mainly within the β chains. Every individual has two alleles at each MHC locus inherited one from each parent. Any individual will therefore express two variants at most at each locus.

This gives a maximum variability for an individual of:

* 6 different variants of MHC class I (2 each of HLA- A, B and C)

* 6 different variants of MHC class II (2 each of HLA- DP, DQ and DR)

Many animal species have fewer loci than the human e.g. ruminants have no MHC class II DP.

**  The variation within MHC class I is entirely on the class I heavy chain

*** The β2m is invariant

** The variation within MHC class II is mainly within the β chains

* Every individual has two alleles at each MHC locus

** One inherited from each parent

** Any individual will therfore express two variants at most at each locus

*** This gives a maximum variability for an individual of:

**** 6 different variants of MHC class I

***** 2 each of HLA- A, B and C

**** 6 different variants of MHC class II

***** 2 each of HLA- DP, DQ and DR

* Many animal species have fewer loci than the human

** E.g. ruminants have no MHC class II DP

==MHC and Disease==

==MHC and Disease==