Genes in two MHC class I regions control recognition of a single rat NK cell allodeterminant

Abstract

We have previously presented evidence suggesting that the non-classical class I region of the rat MHC, RT1.C, encodes polymorphic molecules which induce the cytolytic activity of alloreactive NK cells. Those studies used target cells from a panel of MHC congenic rat strains possessing recombined portions of the RT1a, RT1(l) and RT1(u) MHC haplotypes. We have now examined in addition a set of rat strains bearing MHC haplotypes recombinant between RT1(av1) and RT1(c) and a more complex picture of the MHC control of rat NK alloreactivity has emerged. The expression of a major NK allodeterminant [the allogeneic lymphocyte cytotoxicity (ALC) determinant 2 or ALC-2, defined operationally using cold-target inhibition assays], appears to be under the control of both the RT1.C and the classical class I RT1.A region. Similarly, the alloreactive repertoires of NK cells from these recombinant strains are influenced by elements encoded within these two MHC class I regions. We present a model in which the classical class I autoantigen RT1.A(c) exhibits dominant inhibition of NK cytotoxicity specific for the stimulatory determinant ALC-2 shared by the non-classical class I molecules RT1.C(av1), RT1.Ca and RT1.C(c), and also prevents the deletion of NK cells of this specificity during their development.