alpha 1/alpha 2 domains of H-2D(d), but not H-2L(d), induce "missing self"reactivity in vivo - No effect of H-2L(d) on protection against NK cells expressing the inhibitory receptor Ly49G2

Introduction of the MHC class I transgene H-2D(d) on C57BL/6 (B6) backgroun d conveys NK cell-mediated "missing self" reactivity against transgene-nega tive cells, and down-regulates expression of the inhibitory receptors Ly49A and Ly49G2 in NK cells. We here present an analysis of transgenic mice exp ressing chimeric H-2D(d)/L-d MHC class I transgenes, and show that the alph a 1/alpha 2 domains of H-2D(d) were necessary and sufficient to induce "mis sing self" recognition and to down-modulate Ly49A and Ly49G2 receptors. In contrast, transgenes containing the alpha 1/alpha 2 domains of H-2L(d) indu ced none of these changes, suggesting that not all MHC class I alleles in a host necessarily take part in NK cell education. The lack of effect of the alpha 1/alpha 2 domains of H-2L(d) on NK cell specificity was surprising, considering that both H-2L(d) and H-2D(d) have been reported to interact wi th Ly49G2. Therefore, the role of H-2L(d) for protection against NK cells e xpressing Ly49G2 was re-investigated in a transfection system. In contradic tion to earlier reports, we show that H-2D(d), but not H-2L(d), abolished k illing by sorted Ly49G2(+) NK cells, indicating that H-2L(d) does not inhib it NK cells via the Ly49G2 receptor.