HLA-B62 as a possible ligand for the human homologue of mouse macrophage MHC receptor 2 (MMR2) on monocytes

We previously reported that a population of allograft (H-2DdKd)-induced macrophages (AIM) in C57BL/6 (H-2DbKb) mice exhibited major histocompatibility complex (MHC) haplotype (H-2Dd or H-2Kd)-specific killing of allografts in a macrophage MHC receptor 1 or 2 (MMR1 or 2)-dependent manner. In the present study, we isolated a cDNA encoding a human homologue (83.6% amino-acid identity) of mouse MMR2 from a human cDNA library, the donors of which had never been allografted. The cDNA (2376-bp) encoded a 791-amino-acid polypeptide with a calculated molecular mass of 91 kDa. Unexpectedly, the mRNA was expressed at least in part in peripheral blood mononuclear cells (PBMCs) or monocytes, but not in granulocytes or lymphocytes. The expression varied from volunteer to volunteer: PBMCs from 8 volunteers expressed human MMR2 at similar levels, whereas those from 8 other volunteers showed no or much less expression of it. Flow cytometric analyses revealed that HEK293T cells expressing human MMR2 protein bound fluorescein-labeled HLA-B62, but not A2, A-11, A-24 or B7, with a dissociation constant (= 8.9 × 10− 9 M) and that the interaction was completely inhibited by the addition of R12 mAb specific for mouse MMR2. Similarly, the expression of mouse MMR2 varied from strain to strain in mice: PBMCs from 9 non-H-2Kd, but not from 3 H-2Kd, mice expressed mouse MMR2 specific for H-2Kd.These results suggest that human MMR2 on monocytes may be a novel receptor for HLA-B62.