Ly49G, but not Ly49C/I, is dispensable for diverse antigen-specific memory NK cell responses in H-2d and H-2b mice

Immunological memory is a hallmark of the adaptive immune system. However, considerable evidence indicates that the natural killer (NK) cell subset of innate lymphoid cells also mediates specific memory responses to diverse antigens, including peptides. Even though the existence of NK cell memory is established, the mechanism behind NK cell adaptive responses is yet to be elucidated. Previously, we observed that the Ly49 family of class-I MHC receptors in mice are critical for the formation of adaptive NK cell memory responses. To define the nature of Ly49 involvement in NK cell memory responses, we investigated the contribution of individual Ly49 receptors and their defined class-I MHC ligands. We determined that the Ly49 requirement for the generation of NK memory responses is not uniform. Specifically, Ly49C and/or Ly49I proteins are indispensable for the adaptive NK cell responses as assessed by contact hypersensitivity recall responses to haptens and peptides, in H-2b and H-2d MHC backgrounds. In contrast, the highly expressed inhibitory receptor, Ly49G, did not appear to play any role in NK cell memory responses as determined using antibody-mediated subset depletion and gene-deficient mouse models, even in strains containing known ligands for Ly49G. These findings point to a unique role for Ly49C/I in adaptive NK cell antigen recognition and provide further insight into the mechanism behind adaptive NK cell responses.