Saturday, 19 May 2012

Education: What is the HLA?

The HLA means the Human Leucocyte antigen (HLA) which is also known as the major histocompatilibilty complex (MHC). This region coded on chromosome 6 determines the individuality of each of us. 

This is very differnt between each individual because there are alot of different variants of the molecules that make up the MHC. 

These variants are learnt by the T cells that you produce so that it can recognise who you are and importantly who you aren't so that it can detect and fight infections.  

There are two main components these are MHC class I (HLA-A, HLA-B, HLA-C) and MHC class II (HLA-DR, HLA-DP, HLA-DQ). 

The class  I molecules are made up of a variable chain and an invariant molecule called beta 2 microglobulin. 

The class II molecules are made up of two chains an alpha and a beta chain. 

These meet to have a cleft or a groove between them and inside this cleft sits a peptide (amino acids strung together), which is what T cells recognise
There molecules have different functions related to their structure and how the peptides from the breakdown of proteins are loaded into the MHC molecules

The different molecules have differnt functions but the real biology is to detect pathogens (Viruses and bacteria) inside and outside of the cell.

Whilst peptides are loaded into MHC class I in the endoplasmic reticulum, which is the place where proteins are made, MHC class II cannot be loaded because they have a blocking molecule called the invariant chain. 

This is removed by a molecule called CLIP and then the class II can be loaded with peptide, but this occurs in an endosome in the cytoplasm away from the endpoplasmic reticulum.




There are alot of different variants of each class I and class II chains so you get one set of variants from mum and another from dad and when you can see how many different genetic variants of each molecule then you can see why it can be used for genetic fingerprinting because the full genetic code can and is very different between individuals. 2.9  to the power 17 is about 300 hundred million, trillion different combinations.  
 
We know that the more important genetic variants linking to susceptibility to MS, reside within the MHC. This supports the concept that there is an immune component to the disease. 

One of the most consistent genetic variant linked to MS susceptibility is HLADRB1*1501. This is the first beta (B) chain of  HLA-DR of the first variant of the 15th cluster of variants. HLADQb*0302 is a second variant of the the third cluster of variants of the beta chain of HLA-DQ.  This latter molecule is linked to the development of type 1 diabetes. 

When a protein is broken down it is more likely to associate and load into certain MHC molecules because of their properties such as acid amino acids attrack to basic amino acids. Therefore if a protein is a target for autoimmunity when it breaks down it will associate with certain MHC variants and this is how genetic linkage to disease occurs.

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