Expression Patterns of Killer Cell Immunoglobulin-Like Receptors (KIR) of NK-Cell and T-Cell Subsets in Old World Monkeys

Abstract

The expression of killer cell immunoglobulin-like receptors (KIR) on lymphocytes of rhesus macaques and other Old World monkeys was unknown so far. We used our recently established monoclonal anti-rhesus macaque KIR antibodies in multicolour flow cytometry for phenotypic characterization of KIR protein expression on natural killer (NK) cells and T cell subsets of rhesus macaques, cynomolgus macaques, hamadryas baboons, and African green monkeys. Similar to human KIR, we found clonal expression patterns of KIR on NK and T cell subsets in rhesus macaques and differences between individuals using pan-KIR3D antibody 1C7 and antibodies specific for single KIR. Similar results were obtained with lymphocytes from the other studied species. Notably, African green monkeys show only a low frequency of KIR3D expressed on CD8+ αβT cells. Contrasting human NK cells are KIR-positive CD56bright NK cells and frequencies of KIR-expressing NK cells that are independent of the presence of their cognate MHC class I ligands in rhesus macaques. Interestingly, the frequency of KIR-expressing cells and the expression strength of KIR3D are correlated in γδ T cells of rhesus macaques and CD8+ αβT cells of baboons.

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

“…Specific interactions between KIRs of primates and MHC class I ligands are being identified and monoclonal antibodies against primate KIR proteins are being generated 220, 221. These advances are enabling phenotypic characterization of KIR expression on NK cells and T‐cell subsets in primates and investigation of KIR‐MHC biology in primate models of infectious disease 222, 223, 224…”

Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques – implications for highly complex MHC‐dependent regulation of natural killer cells

“…Rhesus macaque KIR proteins are expressed in a clonal manner, but in contrast to humans the frequencies of rhesus macaque KIR‐expressing NK cells do not appear to depend on the presence of their cognate MHC class I ligands . Specific interactions between macaque KIR3D proteins and MHC class I ligands have been described for rhesus and pig‐tailed macaques (Table ).…”

“…A further characteristic feature of primate (and other mammalian) NK cell receptors is their variegated expression on NK cell and T cell subsets, with most NK cells expressing only a single receptor . As the various receptors are specific for their cognate MHC class I ligands, this expression pattern considerably sharpens the ability of NK cells to recognize diseased cells.…”

γδ T cells for cancer immunotherapy

“…They can be activated by γδ TCR ligands such as phosphoantigens, or by MHC-associated ligands of the activatory receptor killer cell lectin-like receptor subfamily K, member 1 (KLRK1, best known as NKG2D, such as MHC class I polypeptide-related sequence A (MICA), MICB, and various members of the UL16-binding protein (ULBP) family. γδ T cells also express killer-cell immunoglobulin-like receptors (KIRs), which can be either activatory or inhibitory, including killer cell immunoglobulin-like receptor, 2 domains, long cytoplasmic tail, 1 (KIR2DL1) 8 and killer cell immunoglobulin-like receptor, 3 domains, long cytoplasmic tail, 1 (KIR3DL1) 9 . Tumors possess the ability to manipulate this balance to stimulate tolerance by inhibitory signals, including soluble NKG2D ligands, transforming growth factor β1 (TGFβ1), galectin 3 and prostaglandin E 2 (PGE 2 ) 10 , 11 , 12 , 13 Elevated circulating levels of sMICA, sMICB, and sULBP1 might be particularly active against effector γδ T cells, as the latter express high amounts of NKG2D.…”