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Inhibitory receptors specific for MHC class I educate murine NK cells but not CD8αα intestinal intraepithelial T lymphocytes.
The engagement of inhibitory receptors specific for major histocompatibility complex class I (MHC-I) molecules educates natural killer (NK) cells, meaning the improvement of the response of activation receptors to subsequent stimulation. It is not known whether inhibitory MHC-I receptors educate only NK cells or whether they improve the responsiveness of all cell types, which express them. To address this issue, we analyzed the expression of inhibitory MHC-I receptors on intestinal intraepithelial lymphocytes (iIELs) and show that T-cell receptor (TCR)-αβ CD8αα iIELs express multiple inhibitory receptors specific for MHC-I molecules, including CD94/NKG2A, Ly49A, and Ly49G2. However, the presence of MHC-I ligand for these receptors did not improve the response of iIELs to activation via the TCR. The absence of iIEL education by MHC-I receptors was not related to a lack of inhibitory function of these receptors in iIELs and a failure of these receptors to couple to the TCR. Thus, unlike NK cells, iIELs do not undergo an MHC-I-guided education process. These data suggest that education is an NK cell-specific function of inhibitory MHC-I receptors.
Animals, Antigens, CD8/metabolism, Cells, Cultured, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/immunology, Intestinal Mucosa/cytology, Intestinal Mucosa/immunology, Killer Cells, Natural/immunology, Killer Cells, Natural/metabolism, Lymphocyte Activation/genetics, Lymphocyte Activation/physiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Natural Killer Cell/genetics, Receptors, Natural Killer Cell/immunology, Substrate Specificity, T-Lymphocytes/immunology, T-Lymphocytes/metabolism
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