DQ functions in recognizing and presenting foreign antigens (proteins derived from potential pathogens).
But DQ is also involved in recognizing common self-antigens and presenting those antigens to the immune system in order to develop tolerance from a very young age.
DQ mediates autoimmunity by skewing the T-cell receptor (TCR) repertoire during thymic selection.
[1] Carriers of risk serotypes such as DQ8 have a higher proportion of circulating T-cell receptors that may bind insulin, the primary autoantigen in type 1 diabetes.
Serotyping is capable of identifying most aspects of DQ isoform structure and function, however sequence specific PCR is now the preferred method of determining HLA-DQA1 and HLA-DQB1 alleles, as serotyping cannot resolve, often, the critical contribution of the DQ α-chain.
HLA DQ functions as a cell surface receptor for foreign or self antigens.
The immune system surveys antigens for foreign pathogens when presented by MHC receptors (like HLA DQ).
These T-cells, called T-helper cells, can promote the amplification of B-cells which, in turn recognize a different portion of the same antigen.
Alternatively, macrophages and other megalocytes consume cells by apoptotic signaling and present self-antigens.
Self antigens, in the right context, form a regulatory T-cell population that protects self tissues from immune attack or autoimmunity.
This region encoded the subunits for DP,-Q and -R which are the major MHC class II antigens in humans.
In the human population DQ is highly variable, the β subunit more so than the alpha chain.
The variants are encoded by the HLA DQ genes and are the result of single nucleotide polymorphisms (SNP).
Antibodies raised against DQ tend to recognize these functional regions, in most cases the β-subunit.
As a result, these antibodies can discriminate different classes of DQ based on the recognition similar DQβ proteins known as serotypes.
The DQA1*05:01-DQB1*02:01 haplotype is called the DQ2.5 haplotype, and the DQ that results α5β² is the "cis-haplotype" or "cis-chromosomal" isoform of DQ2.5 To detect these potential combinations one uses a technique called SSP-PCR (Sequence specific primer polymerase chain reaction).
This techniques works because, outside of a few areas of Africa, we know the overwhelming majority of all DQ alleles in the world.
The primers are specific for known DQ and thus, if a product is seen it means that gene motif is present.
By examining the structure of these variable regions with different ligands bound (such as the MMDB) one can see which residues come into close contact with peptides and those have side chains that are distal.
Side chains that come close to the peptide can be identified and then examined on the sequence alignments at IMGT/HLA database.
[4] For an explanation of the risk association see:Talk:HLA-DQ#Effects of heterogeneity of isoform pairing-Expanded Involvement of transhaplotypes in disease There is some controversy in the literature whether trans-isoforms are relevant.
At present, the bias of relative isoform frequency toward cis pairing is unknown, it is known that some trans-isoforms occur.
The highest frequencies, by random mating, are expected in Sweden, but pockets of high levels also occur in Mexico, and a larger range risk exists in Central Asia.