Down‐regulated expression of monocyte/macrophage major histocompatibility complex receptors in human and mouse monocytes by expression of their ligands

Summary Mouse monocyte/macrophage major histocompatibility complex ( MHC ) receptor 1 ( MMR 1; or MMR 2) specific for H‐2D d (or H‐2K d ) molecules is expressed on monocytes from non‐ H‐2D d (or non‐ H‐2K d ), but not those from H‐2D d (or H‐2K d ), inbred mice. The MMR 1 and/or MMR 2 is essential for the rejection of H‐2D d ‐ and/or H‐2K d ‐transgenic mouse skin onto C57BL /6 ( H‐2D b K b ) mice. Recently, we found that human leucocyte antigen ( HLA )‐ B 44 was the sole ligand of human MMR 1 using microbeads that had been conjugated with 80 types of HLA class I molecules covering 94·2% (or 99·4%) and 92·4% (or 96·2%) of HLA ‐ A and B molecules of N ative A mericans (or J apanese), respectively. In the present study, we also explored the ligand specificity of human MMR 2 using microbeads. Microbeads coated with HLA ‐ A 32, HLA ‐ B 13 or HLA ‐ B 62 antigens bound specifically to human embryonic kidney ( HEK )293 T or EL ‐4 cells expressing human MMR 2 and to the solubilized MMR 2‐green fluorescent protein ( GFP ) fusion protein; and MMR 2 + monocytes from a volunteer bound HLA ‐ B 62 molecules with a K d of 8·7 × 10 −9   M , implying a three times down‐regulation of MMR 2 expression by the ligand expression. H‐2K d (or H‐2D d ) transgene into C57BL /6 mice down‐regulated not only MMR 2 (or MMR 1) but also MMR 1 (or MMR 2) expression, leading to further down‐regulation of MMR expression. In fact, monocytes from two (i.e. MMR 1 + / MMR 2 + and MMR 1 – / MMR 2 – ) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMR s on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMR s on macrophages toward allografts in tissue.