For instance, it is well known as every individual has 12 group class I and class II HLA allele production because of co-dominance. Each pair of molecules consists of allele products from the father and mother, respectively. But inside of molecules, why don't the alpha chain and beta chain come from the father and mother, respectively?
Dear Shelly Xie,
If you look the coding region for the HLA class II alpha and beta chains, you can see, that they are located in a low distance. Normally, the HLA class II alpha and beta chains from each parental chromosome 6 are expressed together.
In some diseases, like celiac disease, we can see a functional combination between the parental alpha and beta chains (DQA1 and DQB1). The DQB1 beta chains can bind to different DQA1 alpha chains!
-> Crossover hybride HLA molecules
Best regards,
Thomas
N Engl J Med 2000; 343: 702-709. (genomic HLA structure)
Annu Rev Immunol 2011, 29:493-525. (celiac disease)
Dear Shally,
if you are talking about the inheritance of HLA alleles I suggest you to read some basic concept of "linkage disequilibrium" acting at the HLA region; if you see the matter at the protein level, the paternal and maternal alleles can code for momomers which can form heterodimers.
Hope this helps.
Best regards,
Cristina
Inheritance is linked, that's for sure. However, after transcription and translation, the choice of paring between alpha and beta chain depends on the affinity between them, and not on the genetic background.
Cornelis, are MHC chains known to mispair in vivo at all, then? In other Ig genes like TCR and BCR, allelic exclusion is used to make sure that only productively rearranged chains are expressed and that there is only one pair expressed at the cell surface. As far as I can tell, MHC II genes don't do this, so this implies that the chains of each allele bind to only each other...but intuitively that seems like a very leaky mechanism
If you're asking about the association between maternal and paternal alpha and beta chains, this is possible in the case of DP and DQ which give us 8 possible molecules altogether, DR alpha chain is invariant, but many of us have second DRB allele which is expressed, giving up to 4 HLA-DR molecules. Totally, we can have 12 molecules - thanks to promisquity of alpha and beta chains from each locus and second DRB.
I guess, you may have asked about homologous recombinations within maternal and paternal alleles, since this recombination is possible in gametes, allowing for the appearance of non-mendelian offspring distribution in rare cases. But we are not aware if this recombination is possible on the level of individual somatic cells. If this was possible, we wouldn't have MHC-restricted T cells.
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