MD-1 is a secreted glycoprotein that was originally identified as a v-myb-regulated gene from avian myeloleukemia virus-transformed chicken myeloblasts (1). The mouse homologue of chicken MD‑1 (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 Toll-IL-1 R (TIR) domain that defines the IL-1 R/TLR superfamily (2‑4). 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 (4).
Mouse MD-1 cDNA encodes a 162 amino acid (aa) residue precursor protein with a putative 19 aa signal peptide and two potential N‑linked glycosylation sites. It shares 40% and 66% aa sequence identity with chicken and human MD-1 respectively (2, 3). MD-1 is mainly expressed in spleen, and also detectable in liver, brain, thymus, and kidney. MD-1 is required for efficient RP105 cell surface expression and function (2‑5). Cell surface RP105/MD-1 complex, in conjunction with TLR4, mediates the innate immune response to LPS in B-cells. Activation of the RP105 complex has been shown to protect against apoptosis, induce B-cell proliferation and upregulate B7.2, a co-stimulatory molecule (5, 6). Since MD-1 is also expressed in liver and brain where RP105 is absent, it has been speculated that MD-1 can also be associated with other LRR-containing molecules, or have additional functions outside the immune system (6).
