MHC class Ia molecules alone control NK-mediated bone marrow graft rejection

Abstract

Mice with functionally deleted genes encoding MHC class I heavy (H-2Kb, H-2Db) and light (β2-microglobulin) chains were used in bone marrow cell transfer experiments to study the role of class Ia and Ib molecules in NK cell function. Absence of H-2Kb and absence of H-2Db on bone marrow cells resulted in complete and in almost complete NK-mediated rejection, respectively. Absence of either H-2 class Ib (at least when expressed in H-2 class Ia-deficient mice) or cell surface class Ia free heavy chains did not result in bone marrow rejection. Thus, in C57BL / 6 adult mice, the inactivation of NK cells required for bone marrow cell engraftment relies entirely upon-H-2 class Ia molecules. These results imply the existence of an inhibitory receptor which recognizes either directly or indirectly H-2Db molecules and further suggest that in C57BL / 6 mice the NK cells which do not express a H-2Kb specific inhibitory receptor necessarily express an H-2Db-specific one.