Acquisition of External Major Histocompatibility Complex Class I Molecules by Natural Killer Cells Expressing Inhibitory Ly49 Receptors

Abstract

Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. We report that during interactions with cells in the environment, NK cells acquired MHC class I ligands from surrounding cells in a Ly49-specific fashion and displayed them at the cell surface. Ligand acquisition sometimes reached 20% of the MHC class I expression on surrounding cells, involved transfer of the entire MHC class I protein to the NK cell, and was independent of whether or not the NK cell expressed the MHC class I ligand itself. We also present indirect evidence for spontaneous MHC class I acquisition in vivo, as well as describe an in vitro coculture system with transfected cells in which the same phenomenon occurred. Functional studies in the latter model showed that uptake of H-2Dd by Ly49A+ NK cells was accompanied by a partial inactivation of cytotoxic activity in the NK cell, as tested against H-2Dd-negative target cells. In addition, ligand acquisition did not abrogate the ability of Ly49A+ NK cells to receive inhibitory signals from external H-2Dd molecules. This study is the first to describe ligand acquisition by NK cells, which parallels recently described phenomena in T and B cells.

Natural killer (NK)–dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+T cells

“…Trogocytosis is generally thought to be triggered by receptor signaling, and it has been reported that NK cells acquire MHCI and MHCI-related chain B from target cells by using NK cell receptors (NKRs) (21)(22)(23). Therefore, we conducted further studies to determine whether NKR signaling is required for MHCII acquisition.…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…However, our recent work has provided the first evidence of bidirectional membrane molecule transfer between dendritic and T cells in murine system (26). Similarly, new findings on trogocytosis are acquired pertaining to NK cells showing that NK cells can capture the target cell-MHC class I protein both in vitro and in vivo (27)(28)(29) and the virus receptor (CD155) (30) and the membrane fragments (31) from the target cells. Both in human and mouse cells, it was shown that NK cell receptors for MHC class I protein can be transferred to target cells (32), demonstrating a bidirectional membrane transfer.…”

“…Intercellular transfer of proteins can also regulate NK cell functions. Acquisition of MHC class I molecules by NK cells from tumor cells resulted into a reduced NK cytotoxic function in mice (28). In addition, contact between NK cells and target cells, which express NKG2D and MIC respectively, led to intercellular exchange of NKG2D and MIC that correlated with reduction in NKG2D-dependent NK cell cytotoxicity in subsequent interactions (41).…”

The Activating NKG2D Ligand MHC Class I-Related Chain A Transfers from Target Cells to NK Cells in a Manner That Allows Functional Consequences

“…It has recently been established that killer Ig-related receptor (KIR) and their corresponding ligands, class I MHC proteins, exchange between NK cells and target cells in contact (35)(36)(37)(38). To determine whether activating ligands transfer from target cells to NK cells during activating interactions, we stably expressed YFP-tagged MICA, a ligand for the activating NK cell receptor NKG2D, in the EBV transformed B cell line 721.221 (221/MICA-YFP).…”

“…T and B cells acquire peptide/MHC class I proteins and costimulatory molecules or Ag, respectively (33,34). Human, as well as mouse, NK cells acquire cognate MHC class I molecules in vitro and in vivo (35)(36)(37). This transfer is bidirectional, as target cells will take up inhibitory NK cell receptors in the same interactions (38).…”