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PIRs mediate innate myeloid cell memory to nonself MHC molecules

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Science  07 May 2020:
eaax4040
DOI: 10.1126/science.aax4040

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Abstract

Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. It is unknown however whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously upon subsequent encounters. 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.

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