Self-MHC class Ia (RT1-An) protects cells co-expressing the activatory allogeneic MHC class Ib molecule (RT1-Eu) from NK lysis

We have previously shown activation of NK cells via recognition of an allogeneic, non-classical MHC class I molecule, RT1-E-u, In this study we investigated whether a seif-MHC class 1 molecule could protect the allogeneic targets from being recognized and killed by the alloreactive NK (allo NK) cells. NK cells from BN (RT1(n)) rats, primed in vivo by immunization with RT1(u)-expressing cells, manifested cytolytic activity against RT1(u)- as well as RT1(u/lv1)-expressing targets, but not against RT1(u/n)-expressing targets. The absence of cytolytic activity against semiallogeneic targets, i.e. targets expressing self-allotypes, was also valid for allo NK cells from alloimmunized F344 (RT1(lv1)) rats. To analyze the ability of a distinct MHC class I molecule to protect target cells from NK lysis, Rat2 cells transfected with the activating allogeneic MHC class lb, RT1-E-u molecule were also transfected with the self-MHC class la, RT1-Al-n molecule. The allo NK cells from BN rats immunized with RT1(u)-expressing cells were cytolytic against Rat2 transfected with the RT1-E-u molecule. However, the allo NK cells manifested no cytolytic activity against double-transfected Rat2 cells, expressing the RT1-E-u as well as the RT1-A1(n) molecule. We conclude that expression of a self-MHC class la (RT1-A) molecule protects targets from allo NK killing. Furthermore, the NK inhibition via recognition of the self-MHC class la molecule dominates over the activation via recognition of the allogeneic MHC class lb molecule, RT1-E.