A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells

TLDR

NK cell–mediated lysis is regulated by inhibitory receptors for MHC class I, and myelomonocytic cells also express polymorphic homologues that may recognize distinct HLA class I molecules. The study characterizes a novel inhibitory MHC class I receptor, ILT2, expressed on NK, T, B, monocytes, macrophages, and dendritic cells. ILT2 binds MHC class I molecules and delivers a negative signal that inhibits NK and T cell killing, as well as Ca²⁺ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and HLA‑DR. These results suggest that diverse leukocyte lineages use self‑MHC class I recognition as a common strategy to control cellular activation during an immune response.

Abstract

Natural killer (NK) cell–mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)–DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self–MHC class I molecules as a common strategy to control cellular activation during an immune response.