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Crack Para Rhinogold 4.0 17

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What is the fundamental difference between a HLA-DR3/DQ3-restricted T cell and a HLA-DR4/DQ4-restricted T cell?

The website TissMed summarizes this nicely:

CDR3 expression and binding of the TCR with the MHC molecule determines the type of T cell. MHC class II-restricted T cell receptors generally bind to peptide fragments of native proteins presented by MHC class II proteins (for example, DRB3-restricted T cells recognize antigenic peptides from DRB3-allotyped class II molecules).

However, in this paper, Jorgen describes the class II haplotypes as having been described in an “orderly fashion”. I would have thought that the main difference between DR-restricted and DQ-restricted T cells would be their ability to bind MHC class II molecules of different specificities, but Jorgen indicates a difference in the TCR sequences between these DR-restricted and DQ-restricted T cells. I can’t find any description of what this difference might be.
What is the fundamental difference between a HLA-DR3/DQ3-restricted T cell and a HLA-DR4/DQ4-restricted T cell?

A:

All of the DR or DQ alleles are at the extremes of the HLA-DR and HLA-DQ loci. In theory, the “restriction” allele can actually be any of the 20 DRB or 57 DQA/DQB alleles at any given locus. That may seem a lot but consider that a number of DR alleles are very rare or even non-existent in some populations. If you then look at the amino acid sequence, the genes can be quite different. So, while the DR and DQ alleles are clustered at the extremes, they are not completely discrete.
That said, DRB1*04:01/DQB1*06:02 is an extreme DRB1/DQA1/DQB1 haplotype that gives rise to anti-Desmoglein-3 T cells (I can get the reference if you’d like).

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