Inhibitory receptors specific for MHC class I educate murine NK cells but not CD8αα intestinal intraepithelial T lymphocytes

• Published in: Blood Vol. 118; no. 2; pp. 339 - 347
• Main Authors: Taveirne, Sylvie, Filtjens, Jessica, Van Ammel, Els, De Colvenaer, Veerle, Kerre, Tessa, Taghon, Tom, Vandekerckhove, Bart, Plum, Jean, Held, Werner, Leclercq, Georges
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 14.07.2011; Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; CD8 Antigens - metabolism; Cells, Cultured; Hematologic and hematopoietic diseases; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - physiology; Lymphocyte Activation - genetics; Lymphocyte Activation - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Natural Killer Cell - genetics; Receptors, Natural Killer Cell - immunology; Receptors, Natural Killer Cell - metabolism; Receptors, Natural Killer Cell - physiology; Substrate Specificity; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; HLA-System; Hematology; Digestive system; Major histocompatibility system; Rodentia; Gut; Epithelium; Natural killer cell; Vertebrata; Mammalia; Mouse; Animal; T-Lymphocyte; Class I histocompatibility antigen; Biological receptor
• DOI: 10.1182/blood-2011-01-331124
• ISSN: 0006-4971

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.