High impact information on Ly86

• The similarity was attributed to the absence of cell surface RP105 on MD-1-null B cells [1].
• Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide [1].
• We previously reported that MD1, a molecule known to be important in regulation of expression of RP105, also was important in regulating alloimmunity, and that blockade of expression of MD1 diminished graft rejection in vivo [2].
• In addition, blockade of MD1 functional activity in dendritic cells (using anti-MD1 mAbs, MD1 antisense deoxyoligonucleotides, or responder cells from mice with deletion of the MD1 gene), resulted in elevated Treg induction in response to allogeneic stimulation (in vivo or in vitro) in the presence of LPS [2].
• MD1 expression regulates development of regulatory T cells [2].

Biological context of Ly86

• In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation [1].
• The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes [3].
• Blocking MD-1 gene expression inhibits surface expression of CD80 and CD86, but not of OX2 [4].
• Regulation of gene expression of murine MD-1 regulates subsequent T cell activation and cytokine production [4].
• We investigated the effect of treatment with antisense deoxyoligonucleotides or antibodies to MD-1 in vivo on allogeneic and xenogeneic skin graft survival and the immune responses in transplanted mice [5].

Anatomical context of Ly86

• MD-1 is linked to CD14, a "danger receptor complex," and activation of this complex can regulate cell surface expression of CD80/CD86, which signal T cells [4].
• Increased expression of OX2 on dendritic cells (DC) in vivo following preimmunization via the portal vein is also associated with elevated expression of MD-1 [4].
• In addition, MD1 detects flattened subcapsular cells rarely in mouse thymus but frequently in human thymus [6].
• Medullary epithelial cells, identified by the MD1 mAb, were greatly reduced in number and abnormally organized for at least 4 mo after TLI [7].
• Grafts from MD-1-treated mice showed little lymphocyte infiltration, and no signs of graft necrosis [5].

Analytical, diagnostic and therapeutic context of Ly86

• PROBLEM: At least two dendritic cell-associated molecules have been shown to contribute to the successful outcome of organ and tissue allografts in mice, namely CD200 and MD-1 [8].
• Anti-CD200 antibody raised the abortion rate to predicted levels, and infusion of a CD200 immunoadhesin reduced the abortion rate, as did an anti-MD-1 antibody [8].

References