Talk:HLA-DQ
From Wikipedia, the free encyclopedia
 |
This article is within the scope of the Molecular and Cellular Biology WikiProject. To participate, visit the WikiProject for more information. The WikiProject's current monthly collaboration is focused on improving Restriction enzyme. |
||
| B | This article has been rated as B-Class on the assessment scale. |
||
| Mid | This article is on a subject of mid-importance within molecular and cellular biology. | ||
|
Article Grading: The article has been rated for quality and/or importance but has no comments yet. If appropriate, please review the article and then leave comments here to identify the strengths and weaknesses of the article and what work it will need. |
|||
[edit] Effects of heterogeneity of isoform pairing-Expanded
| HLA | DQB1 | ||
|---|---|---|---|
| allele | (m) | (p) | |
| DQA1 | (m) | αmβm (Cis m) | αmβp (Trans) |
| (p) | αpβm (Trans) | αpβp (Cis p) | |
| Result: 2 Cis, αmβm & αpβp, isoforms and 2 trans,αmβp & αpβm. | |||
Each combination of DQA1 allele gene product with each combination of DQB1 'gene' product can potentially recombine to produce one isoform. DQ genes are highly variable in the human population. In a typical population there are many DQ alpha and beta, most isoforms are not common. The more common isoforms result from 'cis' haplotypes (Tables above and to the right), but the less common protein isoforms are the result of trans-chromosomal or trans-haplotype isoform pairing.
| HLA | DQB1 | ||
|---|---|---|---|
| allele | *0202 | *0301 | |
| DQA1 | *0201 | α²β² | α²β301 |
| *0505 | α5β² | α5β301 | |
For example, suppose one has the (for simplicity let us remove the HLA DQ prefix) A1*0201:B1*0202 and A1*0505:B1*0301 haplotypes, one 'cis-haplotype' isoforms that one would share with many other people would be DQα²β² and the other α5β301. The other two isoforms are α²β301 and α5β². In this case the α5β² is the same isoform as the cis-DQ2.5 isoform and has the same risks for disease. In theory random pairing the resulting isoforms are at a ratio of 1:1:1:1. [Note some isoforms have shortened superscript, like α³, in some cases there is only one isoform for that DQA1*0X type, in other cases the processed products are functionally identical.]
Functional similarity of subunits is largely determined by residues within the binding pocket, and particularly those with side chains in positions that can interact with the peptides (see illustration of DQ2.5 with gliadin peptide in the binding pocket) Only the amino acids that are in the binding pocket and also have side chains that point in the direction of the peptide (yellow, in this case wheat gliadin peptide) more directly affect binding. Those that stick out of either DQ α5 or DQ β² subunits but not interfering with the binding of peptides can be altered without altering binding. These changes might alter T-cell recognition or have more basal forms of functional changes.
| HLA | DQB1 | ||
|---|---|---|---|
| allele | *0202 | *0201 | |
| DQA1 | *0201 | α²β² | α²β² |
| *0501 | α5β² | α5β² | |
| Result: 2 Isoforms: 50% α5β² and 50% α²β² | |||
homozygotes and double homozygotes. Homozygotes at DQ loci can change risk for disease. In the case of celiac disease DQ2.5/DQ2 homozygotes are several times more likely to have celiac disease versus DQ2.5/DQX individuals. The risk is elevated because when α5 is undergoing subunit pairing it has no choice but to bind β² and since randomly α5 represents 1/2 of alpha chain the dimer α5β² also results in 1/2 of DQ, which is more than the 1/4 expected for heterozygote pairing. In DQ2.5/2.5 individuals neither alpha or beta has isoform variants so all of the DQ is α5β². Therefore the level of genetic heterogeneity in the individuals determines whether one can produce 1, 2 or 4 isoforms.
| HLA | DQB1 | ||
|---|---|---|---|
| allele | *0201 | *0201 | |
| DQA1 | *0501 | α5β² | α5β² |
| *0501 | α5β² | α5β² | |
| Result: 1 Isoform: 100% α5β² | |||
