Homologies between cell interaction molecules controlled by major histocompatibility complex- and Igh-V-linked genes that T cells use for communication; both molecules undergo "adaptive" differentiation in the thymus.

We have previously described two types of immunoregulatory interactions between T cell subsets; in one an Ly-1; I-J+ inducer cell makes a soluble product (Ly-1 T suppressor inducer factor, TsiF) that is also I-J+ and which activates the effector cells of a suppressor circuit. Under normal circumstances the Ly-1 TsiF activity is restricted by Igh-V-linked genetic polymorphisms. However, we now find the genotype of the inducer cell does not control this restriction. The inducer cell acquires a new Igh-V-linked self repertoire if it ("adaptively") differentiates in an appropriate F1 radiation chimera or in an F1 thymus graft in a homozygous nude mouse. Conversely, cells from F1 mice cannot acquire this "dual" self repertoire if the host in which they differentiate does not express the relevant selecting structure(s). A previously demonstrated H-2-restricted suppressor factor (Ly-2 T suppressor factor) has also been examined and it is shown that this molecule is subject to the same differentiation constraints as is the Igh-V-linked restricted factor except, or course, in this case H-2-linked genes are the "restricting" elements. Thus, Igh-V restrictions are related to major histocompatibility complex (MHC) restrictions in the parameter that has been termed "adaptive" differentiation. The results also imply that the I-J-marked Igh-V-linked self recognition molecule(s) has a variable and constant region, since the adaptively differentiated molecules that show a new self recognition specificity retain the genetic I-J polymorphism of the mice that supplied the bone marrow precursor cells and not the one of the thymus in which they differentiated. It may be considered surprising to find a structure in the thymus that acts to select MHC-positive molecules that see Igh-V-linked structures as self. The F1 into parent experiments make it unlikely that the thymus is passively armed by circulating molecules that might act as the selecting elements. Since there is such a striking parallelism in the "adaptive" differentiation of cells that recognize Igh-V and MHC as self, one must consider the possibility that Igh-linked gene products are expressed by cells in the thymus and function there to select for those Ly-1 TsiF producer cells that can recognize these Igh-V-linked cell interaction structures as self.