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The generation of knockout mice demonstrated that noncytotoxic CD4+, but not cytotoxic CD8+, T cells were essential for the rejection of skin or organ allografts. Earlier we reported that allograft‐induced macrophages (AIM) in mice lysed allografts with H‐2 haplotype specificity, implying screening of grafts by AIM. Here, we isolated a cDNA clone encoding a novel receptor on AIM (H‐2Db) for an allogeneic major histocompatibility complex (MHC) class I molecule, H‐2Dd, by using H‐2Dd tetramer and a monoclonal antibody (mAb; R15) specific for AIM. The cDNA (1,181‐bp) encoded a 342‐amino acid polypeptide with a calculated molecular mass of 45 kDa and was found to be expressed on AIM, but not on resident macrophages or other cells, infiltrating into the rejection site. HEK293T cells transfected with this cDNA reacted with R15 mAb and H‐2Dd, but not H‐2Ld, H‐2Kd, H‐2Db, H‐2Kb, H‐2Dk, or H‐2Kk, molecules; and the H‐2Dd binding was suppressed by the addition of R15 or anti‐H‐2Dd mAb. AIM yielded a specific saturation isotherm in the presence of increasing concentrations of H‐2Dd, but not H‐2Db or H‐2Dk, molecules. The dissociation constant of AIM toward H‐2Dd tetramers was 1.9×10–9 M; and the binding was completely inhibited by the addition of R15 or anti‐H‐2Dd mAb. These results reveal that a novel receptor for an allogeneic H‐2Dd molecule was induced on effector macrophages responsible for allograft (H‐2d) rejection in H‐2b mice.
Microbiology and Immunology – Wiley
Published: Jan 1, 2006
Keywords: ; ; ;
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