Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer Look

Abstract

The Natural Killer (NK) cell population is composed of subsets of varying sizes expressing different combinations of inhibitory receptors for MHC class I molecules. Genes within the NK gene complex, including the inhibitory receptors themselves, seem to be the primary intrinsic regulators of inhibitory receptor expression, but the MHC class I background is an additional Modulating factor. In this paper, we have performed a parallel study of the inhibitory receptor repertoire in inbred mice of the C57Bl/6 background and in a cohort of 44 humans. Deviations of subset frequencies from the “product rule (PR),” i.e., differences between observed and expected frequencies of NK cells, were used to identify MHC-independent and MHC-dependent control of receptor expression frequencies. Some deviations from the PR were similar in mice and humans, such as the decreased presence of NK cell subset lacking inhibitory receptors. Others were different, including a role for NKG2A in determining over- or under-representation of specific subsets in humans but not in mice. Thus, while human and murine inhibitory receptor repertoires differed in details, there may also be shared principles governing NK cell repertoire formation in these two species.

The Abl‐1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education

“…We used a multicolour flow cytometry panel to investigate the expression pattern of Ly49C, Ly49I, Ly49A, Ly49G2 and NKG2A in Cre+/− c‐Abl fl/fl and Cre+/− c‐Abl +/fl NK cells. We focussed on NK cells expressing the self‐specific receptors Ly49C and Ly49I as their only receptor, as those subsets are most clearly subject to NK cell education in mice expressing H2K b , in which their frequencies are increased compared to mice lacking MHC class I . Our analysis revealed no major differences in the frequency of NK cells expressing any of these five receptors as their only receptor (Fig.…”

Natural killer cells unleashed: Checkpoint receptor blockade and BiKE/TriKE utilization in NK-mediated anti-tumor immunotherapy

“…Since healthy cells express a normal compliment of MHC-I molecules even though they may constitutively express some activating ligands, the inhibitory signal will dominate, resulting in the inhibition of NK function and maintenance of tolerance. It is important to note that NK cells as a population are highly variegated in terms of their inhibitory receptor expression[44]. Not every NK cell expresses every inhibitory receptor.…”

Newtonian cell interactions shape natural killer cell education

“…It has been debated whether there are additional, cellular mechanisms involved in shaping the NK cell repertoire to further promote self‐tolerance. Several models of positive and negative selection have been proposed including the sequential selection model and the two‐step selection model . Both models suggest that interactions with MHC during NK cell development results in selection of cells that express self‐specific inhibitory receptors.…”