Impaired anti-viral T cell responses due to expression of the LY49A inhibitory receptor

Inhibitory receptors specific for alleles of MHC class I proteins play an i mportant role in determining the reactivity and specificity of NK cells. To determine whether these receptors are also able to regulate T cell functio ns we have studied anti-viral immune responses in mice transgenic for a cla ss I-specific inhibitory receptor, Ly-49A, Although nontransgenic mice expr ess Ly49A primarily on NK cells and some T cells, the Ly49A transgenic mice express Ly49A on all lymphocytes, including T cells. We have assessed the activation, expansion, cytokine production, and cytotoxic activity of CD8 T cells in both transgenic and nontransgenic mice following infection with l ymphocytic choriomeningitis virus. As expected, nontransgenic mice made a p otent virus-specific CD8 T cell response following virus infection. However , as measured in cytolysis assays and by cytokine production, virus-specifi c CD8 T cell activity was reduced in Ly49A transgenic mice. This inhibition was largely, but not always exclusively dependent upon the presence, eithe r in vivo or in vitro, of the Ly49A ligand, H-2D(d). Strikingly Ly49Ah tran sgenic mice have reduced capacity to control infection with the virulent ly mphocytic choriomeningitis virus variant clone 13. Overall, these studies d emonstrate that expression of killer inhibitory receptors can modulate anti -viral T cell responses in vivo and in vitro.