MHC class II diversity and specificity
Unlike MHC class I, which is expressed on all our cells, MHC class II molecules are highly expressed on a small number of specialised cells, known as antigen presenting cells. The MHC class II molecules that our cells express are extremely different, or diverse, between unrelated individuals. Let's watch this video and consider how this happens.
How did the MHC class II molecule end up so different in two individuals?
Firstly, MHC molecules are highly polygenic, meaning there are several gene families or gene loci as we saw in the video. We saw HLA-DM, HLA-DO, HLA-DP, HLA-DQ and HLA-DR, all known as MHC class II isotypes. Each molecule is made up of an alpha and beta protein chain. The main function of HLA-DP, HLA-DQ and HLA-DR is the presentation of antigen to CD4+ helper T cells. As we will see later, HLA-DO and HLA-DM act as chaperone proteins, ensuring correct loading of peptide and presentation by the other isotypes for T cell interaction.
Secondly, the HLA-DP, HLA-DQ and HLA-DR molecules are highly polymorphic. A polymorphism is a nucleotide change in the DNA of the individual. This change can affect the affinity with which a molecule binds antigen, or even what antigen it interacts with. The alternative forms of the genes are referred to as allotypes. Different polymorphisms occur in different people, and the set of polymorphisms or alleles that you have is referred to as a haplotype. An individual inherits one haplotype from each parent. A further increase in diversity is achieved by MHC genetic recombination, or crossover, occurring between parental haplotypes during meiosis. This generates new allelic combinations. All these factors make it highly unlikely that two unrelated people will have matching MHC profiles.
So if that was diversity what is specificity?
Since MHC class II molecules act as antigen presenting structures and T cells will only recognise antigen in combination with an MHC molecule, the particular set of MHC molecules an individual has, and the haplotypes that are inherited, influences the repertoire of antigen to which the T cells will respond. Each T cell has only one T cell receptors (TCR) that is specific for one combination of MHC class II and peptide, and there you have specificity!