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B6 Strain Ly49I Inhibitory Gene Expression on T Cells in FVB.Ly49I^B6 Transgenic Mice Fails to Prevent Normal T Cell Functions^{1 ,2}

Margaret A. Morris^*,, Jingxuan Liu^*,, Veera Arora^*, Thaddeus C. George^*,, Jennifer Klem^*,, John D. Schatzle^*, Vinay Kumar and Michael Bennett^3,*

^* Department of Pathology, Laboratory of Molecular Pathology, and Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and Department of Pathology, University of Chicago, Chicago, IL 60637

Inhibitory Ly49 receptors expressed on NK cells provide a mechanism for tolerance to normal self tissues. The immunoregulatory tyrosine-based inhibitory motifs present in some Ly49s are able to transmit an inhibitory signal upon ligation by MHC class I ligands. In our system, as well as others, mice transgenic for inhibitory Ly49 receptors express these receptors on both NK and T cells. FVB (H2^q) mice transgenic for the B6 strain Ly49I (Ly49I^B6) express the inhibitory Ly49 receptor on the surface of both T and NK cells. Although Ly49I functions to prevent NK-mediated rejection of H2^b donor bone marrow cells in this transgenic mouse strain, the T cells do not appear to be affected by the expression of the Ly49I transgene. FVB.Ly49I T cells have normal proliferative capabilities both in vitro and in vivo in response to the Ly49I ligand, H2^b. In vivo functional T cell assays were also done, showing that transgenic T cells were not functionally affected. T cells in these mice also appear to undergo normal T cell development and activation. Only upon stimulation with suboptimal doses of anti-CD3 in the presence of anti-Ly49I is T cell proliferation inhibited. These data are in contrast with findings in Ly49A, and Ly49G2 receptor transgenic models. Perhaps Ly49I-H2^b interactions are weaker or of lower avidity than Ly49A-H-2D^d interactions, especially in T cells.

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