H-2Dp transgene alters natural killer cell specificity at the target and effector cell levels. Comparison with an H-2Dd transgene
Sentman, C.L.; Olsson-Alheim, M.Y.; Lendahl, U.; Kärre, K.
Journal of Immunology 156(7): 2423-2429
1996
ISSN/ISBN: 0022-1767 PMID: 8786300 Document Number: 466939
The expression of MHC class I molecules is an important determinate of natural killer (NK) cell specificity. The missing self hypothesis proposes that NK cells express receptors for self-MHC class I molecules so that target cells that share MHC class I alleles with the NK cells are not killed by those NK cells. However, some effector cells fail to kill some allogeneic target cells suggesting that shared motifs between different MHC class I alleles can interact with the effector cell class I receptors and prevent lysis. We have used transgenic mice to critically 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) transgenic mice. The data indicate that H-2DP and H-2D-d confer similar protection and specific lysis, such that NK cells from either of the H-2DP or H-2D-d transgenic mice kill nontransgenic target cells yet they do not kill either of the transgenic target cells. The expression of an H-2DP transgene also provides protection for C57BL/6 lymphoblasts 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 through a shared motif recognized by the same receptor, or different motifs recognized by different, but co-expressed receptors.