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Normally HLA molecules present cellular and extra cellular proteins to the immune system; presumably the proteins in this case are where antibody /t-cells etc bind.

But when an organ is transplanted to a HLA incompatible recipient, are they binding to the HLA molecule itself? If antibody response was reliant on the proteome expressed in and around the cell HLA incompatibility wouldn't be such a problem.

What about auto immune diseases?

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  • $\begingroup$ Your question is both unclear and quite broad. "presumably the proteins in this case are where antibody /t-cells etc bind." Please expand on this, I really don't know what you mean. "But when an organ is transplanted to a HLA incompatible recipient, are they binding to the HLA molecule itself?" What do you mean by they? "If antibody response was reliant on the proteome expressed in and around the cell HLA incompatibility wouldn't be such a problem." Why do you think that? "What about auto immune diseases?" What about them? Please edit your question to make it clearer. $\endgroup$ – MattDMo Dec 6 '16 at 18:34
  • $\begingroup$ @MattDMo the question is pretty clear, he's using correct terminology for the topic $\endgroup$ – iayork Dec 6 '16 at 18:40
  • $\begingroup$ @iayork I'm an immunologist, and I don't really think it's clear at all. In the first sentence, the OP is mixing antibody and HLA/TCR epitopes, and it's not clear which is being discussed where. "are they binding..." is definitely unclear, I don't know what "they" is. I don't understand the reasoning behind the 2nd sentence in the 2nd paragraph. Finally, the last sentence is completely apropos of nothing - what about autoimmunity? The whole thing is unclear and far too broad. $\endgroup$ – MattDMo Dec 6 '16 at 18:47
  • $\begingroup$ Seems clear to me (also an immunologist). He's asking how transplant non-self MHC is recognized (peptide dependent or not) and how autoimmune MHC is recognized (peptide dependent or not). Good questions, if rather basic, and worth addressing. $\endgroup$ – iayork Dec 6 '16 at 18:49
  • $\begingroup$ @mattdmo you rightly picked up on my confusion. I work with hla antibody, but am a mathematician by background. Most of the material I can find doesn't seem to make clear where the epitopes are located. I am not sure if hla antibody bind to the same epitopes as the t cells or to others entirety. So if you want more clarity, I am interested in the locations of the binding sites of either. $\endgroup$ – Abijah Dec 6 '16 at 23:14
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T cells in a graft see both non-self peptides associated with the non-self HLA molecules, and can also see the non-self HLA molecules regardless of peptide. (MHC is a broader term than HLA, and I will use MHC here.)

Surface expression of CD4 or CD8 is commonly used to identify T-cell subsets that recognize antigen presented by class II MHC or class I MHC, respectively. This holds true for T cells that respond to allogeneic MHC molecules that are directly recognized as foreign, as well as peptides from allogeneic MHC molecules that are indirectly presented by self MHC molecules.

--Contrasting Alloreactive CD4+ and CD8+ T Cells: There's More to It Than MHC Restriction

Recall that as T cells mature in the thymus, they undergo negative selection such that those T cells that spontaneously recognize self MHC molecules are deleted, but there's also positive selection that ensures the T cells can recognize MHC features in general. That leaves many T cells that could spontaneously recognize slightly different MHC molecules (i.e. non-self) that are not deleted. That means that in a transplant, there are a large number of T cells that can recognize the non-self MHC in a non-peptide-dependent manner. There's also a much smaller number that can interact with the non-self-MHC but only in a peptide-dependent manner; this is just by chance, in that that particular T cell receptor happened to have the shape that sees that non-self-MHC and the peptide.

As for autoimmunity, that's all peptide-dependent, as far as we know, barring some of the really horrendous infant-onset autoimmunities that result from improper T cell maturation in the thymus.

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