Major histocompatibility complex (MHC) class I K b D b 2y2 deficient mice possess functional CD81 T cells and natural killer cells

We obtained mice deficient for major histo- compatibility complex (MHC) molecules encoded by the H-2K and H-2D genes. H-2 K b D b 2y2 mice express no detectable classical MHC class I-region associated (Ia) heavy chains, al- though b2-microglobulin and the nonclassical class Ib proteins examined are expressed normally. K b D b 2y2 mice have greatly reduced numbers of mature CD81 T cells, indicating that selection of the vast majority (>90%) of CD81 T cells cannot be compensated for by b2-microglobulin-associated molecules other than classical H-2K and D locus products. In accord with the greatly reduced number of CD81 T cells, spleen cells from K b D b 2y2 mice do not generate cytotoxic responses in primary mixed-lymphocyte cultures against MHC-disparate (allogeneic) cells. However, in vivo priming of K b D b 2y2 mice with allogeneic cells resulted in strong CD81 MHC class Ia-specific allogeneic responses. Thus, a minor population of functionally competent peripheral CD81 T cells capable of strong cytotoxic activity arises in the complete absence of classical MHC class Ia mole- cules. K b D b 2y2 animals also have natural killer cells that retain their cytotoxic potential.