Donor SIRP-α polymorphisms: widening the innate-to-adaptive continuum in allograft rejection

In the usual paradigm, self:nonself recognition is attributed to calls of the adaptive immune system, owing to variations in specialized genes encoded within the major histocompatibility complex loci. However, an increasing body of data has shown that cells of the innate immune system also have self:nonself recognition functions relevant to organ transplantation, and this trait may derive from genes located outside the major histocompatibility complex loci. A recent publication identifies the donor SIRP-α gene as a non-major histocompatibility complex locus responsible for nonself recognition by monocytes, with variability resulting in changes in the surface interaction of SIRP-α with its ligand CD47.