H-2D(P) TRANSGENE ALTERS NATURAL-KILLER-CELL SPECIFICITY AT THE TARGET AND EFFECTOR CELL LEVELS - COMPARISON WITH AN H-2D(D) TRANSGENE

The expression of MHC class I molecules is an important determinate of natural killer (NK) cell specificity, The missing self hypothesis pro poses that NK cells express receptors for self-MHC class I molecules s o that target cells that share MHC class I alleles with the NK cells a re not killed by those NK cells, However, some effector cells fail to kill some allogeneic target cells suggesting that shared motifs betwee n different MHC class I alleles can interact with the effector cell cl ass I receptors and prevent lysis, We have used transgenic mice to cri tically assess whether different MHC class I alleles can exert common influences on NK cell specificity at the host/effector and target cell levels, The specificity of NK cells have been compared between C57BL/ 6 (H-2(b)) mice and B6DP (H-2(b), H-2D(p)) and D8 (H-2(b), H-2D(d)) tr ansgenic mice, The data indicate that H-2D(p) and H-2D(d) confer simil ar protection and specific lysis, such that NK cells from either of th e H-2D(p) or H-2D(d) transgenic mice kill nontransgenic target cells y et they do not kill either of the transgenic target cells, The express ion of an H-2D(p) transgene also provides protection for C57BL/6 lymph oblasts from allogeneic BALB/c (H-2(d)) NK cells, Furthermore, H-2D(p) and H-2D(d) transgenic target cells are lysed to a similar extent by H-2(k) effector cells, These data suggest that H-2D(p) and H-2D(d) may be able to inhibit the same NK cell population, This may occur throug h a shared motif recognized by the same receptor, or different motifs recognized by different, but co-expressed receptors.