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

Abstract

Mouse monocyte/macrophage major histocompatibility complex (MHC) receptor 1 (MMR1; or MMR2) 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 MMR1 and/or MMR2 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)-B44 was the sole ligand of human MMR1 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 Native Americans (or Japanese), respectively. In the present study, we also explored the ligand specificity of human MMR2 using microbeads. Microbeads coated with HLA-A32, HLA-B13 or HLA-B62 antigens bound specifically to human embryonic kidney (HEK)293T or EL-4 cells expressing human MMR2 and to the solubilized MMR2-green fluorescent protein (GFP) fusion protein; and MMR2(+) monocytes from a volunteer bound HLA-B62 molecules with a Kd of 8·7 × 10(-9) M, implying a three times down-regulation of MMR2 expression by the ligand expression. H-2K(d) (or H-2D(d) ) transgene into C57BL/6 mice down-regulated not only MMR2 (or MMR1) but also MMR1 (or MMR2) expression, leading to further down-regulation of MMR expression. In fact, monocytes from two (i.e. MMR1(+) /MMR2(+) and MMR1(-) /MMR2(-) ) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMRs on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMRs on macrophages toward allografts in tissue.