Strong histocompatibility and cell-mediated cytotoxic effects of a single Mls difference demonstrated using a new congenic mouse strain.

In vivo and in vitro effects of incompatibility at the Mls locus have been studied utilizing a recently created congenic mouse strain. Results obtained with skin grafts were compared to those obtained in the mixed lymphocyte reaction (MLR) and cell-mediated cytotoxicity assays. The in vitro responsiveness of cells from skin-grafted mice was compared to that of cells from corresponding ungrafted mice. The results showed that: (a) Mlsa, strongly stimulatory in primary MLR, has a weak effect on skin graft rejection; specific in vivo preimmunization against Mlsa increases and accelerates the rejection of skin grafts, but abrogates the responsiveness in MLR; and (b) incompatibility for Mlsb, nonstimulatory in primary MLR, induces relatively rapid rejection of 100% of skin grafts; this rejection is dramatically accelerated by specific in vivo preimmunization and is followed by activation of helper and cytotoxic cells. Results obtained in the cell-mediated cytotoxicity assay suggest that the recognition of Mlsb determinants is H-2-restricted. Finally, the rejection of skin grafts incompatible for numerous non-H-2 loci is delayed by an additional incompatibility for Mlsb, suggesting that Mlsb decreases the response to other non-H-2 antigens, thus acting as a suppressor and/or competitor antigen. We conclude that, in contrast with previous findings, Mls incompatibility may have a strong effect on skin graft rejection, depending on the allelic combination involved, and, after in vivo immunization, Mlsb activates cell-mediated proliferative and cytotoxic responses and definitely is not "silent". The importance of the histocompatibility effects of Mls determinants and the variety of its biological functions are much in favor of the existence of a polymorphic and complex system capable of activating different cell subsets.