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

Introduction of the MHC class I transgene H-2D super(d) on C57BL/6 (B6) background conveys NK cell-mediated "missing self" reactivity against transgene-negative cells, and down-regulates expression of the inhibitory receptors Ly49A and Ly49G2 in NK cells. We here present an analysis of transgenic mice expressing chimeric H-2D super(d)/L super(d) MHC class I transgenes, and show that the alpha 1/ alpha 2 domains of H-2D super(d) were necessary and sufficient to induce "missing self" recognition and to down-modulate Ly49A and Ly49G2 receptors. In contrast, transgenes containing the alpha 1/ alpha 2 domains of H-2L super(d) induced 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 super(d) on NK cell specificity was surprising, considering that both H-2L super(d) and H-2D super(d) have been reported to interact with Ly49G2. Therefore, the role of H-2L super(d) for protection against NK cells expressing Ly49G2 was re-investigated in a transfection system. In contradiction to earlier reports, we show that H-2D super(d), but not H-2L super(d), abolished killing by sorted Ly49G2 super(+) NK cells, indicating that H-2L super(d) does not inhibit NK cells via the Ly49G2 receptor.