MD-1

MD1 is a secreted glycoprotein that was originally identified as a v-myb-regulated gene from avian myeloleukemia virus-transformed chicken myeloblasts. The mouse homologue of chicken MD1 (also known as lymphocyte antigen 86) was subsequently discovered as a molecule that is associated with RP105, a type I transmembrane glycoprotein with extracellular leucine rich repeats (LRR) typically found in Toll-like receptor (TLR) family members. However, RP105 has a short cytoplasmic tail and lacks the TollIL1 R (TIR) domain that defines the IL1 R/TLR superfamily. RP105 plays an important role in B-cell activation by bacterial lipopolysaccharide (LPS) . It is expressed primarily on mature B cells, dendritic cells and macrophages. Mouse MD1 cDNA encodes a 162 amino acid (aa) residue precursor protein with a putative 19 aa signal peptide and two potential Nlinked glycosylation sites. It shares 40% and 66% aa sequence identity with chicken and human MD1 respectively. MD1 is mainly expressed in spleen, and also detectable in liver, brain, thymus, and kidney. MD1 is required for efficient RP105 cell surface expression and function. Cell surface RP105/MD1 complex, in conjunction with TLR4, mediates the innate immune response to LPS in Bcells. Activation of the RP105 complex has been shown to protect against apoptosis, induce Bcell proliferation and upregulate B7.2, a costimulatory molecule. Since MD1 is also expressed in liver and brain where RP105 is absent, it has been speculated that MD1 can also be associated with other LRR-containing molecules, or have additional functions outside the immune system.