Paired immunoglobulin-like receptors mediate innate memory to non-self MHC molecules

Abstract: Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. It is not known however whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously upon a second encounter. Here, we show that murine monocytes and macrophages acquire memory specific to MHC-I antigens and identify paired immunoglobulin-like receptors-A (PIR-A) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes. Data purpose: Targeting monocyte and macrophage receptors that detect MHC antigens blocks innate immune memory and attenuates transplant rejection Overall design: splenic monocytes from B6, BALB, C3H mice at 1wk and 4wk post immunization