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

Blood. 2011 Jul 14;118(2):339-47. doi: 10.1182/blood-2011-01-331124. Epub 2011 May 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8 Antigens / metabolism
  • Cells, Cultured
  • 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
  • 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

Substances

  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Histocompatibility Antigens Class I
  • Receptors, Natural Killer Cell