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A few days ago I read about MHC1 knockout pigs for organ transplantation research. I was just wondering, is it enough to knock out MHC1 in the donor (lets say from same species, pig to pig) for successful transplantation?

I understand that someone without MHC1 is more sensitive to viruses, cancer, to NK and more. But the study pigs lived fine, so in theory it is possible to have knockout MHC1 and survive. But is it enough for successful transplantation from one pig (donor with knockout) to another (fully healthy, normal pig) ?

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No, MHCII mismatch can also lead to transplant rejection, though through different mechanisms. CD8+ Tcells (that recognize class I) may become activated and directly kill donor cells*, and some NK subtypes can see the lack of self MHCI and also induce cell death.

MHCII mismatch on antigen presenting cells (APCs) brought along in the tissue may activate CD4+ (helper) Tcells, which do not kill directly. However, they can secrete a lot of pro-inflammatory cytokines which will make a generally hostile environment, and can also activate b-cells to produce antibodies against minor histocompatibility loci.

As to your other question, lacking MHCI entirely would be really rough on an animal in the wild, but under laboratory conditions where pathogens can be managed a bit more, it doesn't matter so much. It's the same reason we can keep mice that have gross immunological deficiencies alive, where humans with the same defects would be screwed.

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  • $\begingroup$ What about MHCII ? It's not on the organ. Also you talking about " lack of self MHCI and also induce cell death" but that is not the question. Also it's wrong cause pigs live well. $\endgroup$ – Robertos Jul 11 '15 at 13:04
  • $\begingroup$ It's rather snide to say "You're wrong they live well" without having ever linked the paper showing this. Without the paper we don't know how far out they were followed, what immunosuppression regimes they may have been given (or what pre-treatment of the organ, etc), or how closely related the pigs were. All of these factors and more can effect the probability of transplant rejection. Also, the organs almost certainly DO have MHCII on resident myeloid cells. Invading myeloid cells will also have MHCII and have the potential to initiate an adaptive response against the transplant. $\endgroup$ – InactionPotential Jul 11 '15 at 13:29
  • $\begingroup$ @VGranin - you're right, MHCII isn't on the organ tissue cells, but it's hard to remove all of the APCs from a graft. Modern transplant protocols do work to remove some of them, but it's not 100%. You asked about using MHCI knockouts as donors, I'm saying that an organ that completely lacks MHCI may be targeted by NK cells. $\endgroup$ – kevbonham Jul 11 '15 at 14:49
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    $\begingroup$ It's an interesting paper, but there are some limitations to your understanding re: they live well. The paper says at the time of publication they were 7 mo old. It does not describe were they are kept, but likely in a highly controlled research facility. For comparison, we keep a number of strains of immunodeficient mice in our facility that wouldn't last a week outside. They are at lower risk of serious infection than your everyday farm/wild pig. $\endgroup$ – InactionPotential Jul 12 '15 at 23:54
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    $\begingroup$ Also, regarding NK cell killing and lack of MHC-I: NK cells undergo a maturation process to a so-called "licensed phenotype" (licensed to kill, ha ha). Immature NK cells are poorly capable/incapable of killing other cells. Maturation into an effective killer involves a process that requires MHC-I expression (based on numerous mouse studies, likely applies here). In animals that do not have MHC-I, the NK cells likely never develop the potential to kill MHC-I negative cells. So they are protected from their own NKs, but licensed foreign NK cells (as in a transplant) could still kill them. $\endgroup$ – InactionPotential Jul 12 '15 at 23:58

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