Anti-BTN2A1 polyclonal antibody

The MHC-encoded butyrophilin, BTN2A1, is a cell surface glycoprotein related to the extended family of B7 costimulatory molecules. BTN2A1 mRNA was expressed in most human tissues, but protein expression was significantly lower in leukocytes. An Ig-fusion protein of BTN2A1 bound to immature monocyte-derived dendritic cells. Binding diminished upon MoDC maturation and no binding was detected to Langerhans cells. Induction of the counterreceptor was IL-4 dependent and occurred early during dendritic cell differentiation. The interaction required the presence of Ca2+ and was mediated by high-mannose oligosaccharides. These properties matched DC-SIGN, a DC-specific HIV-1 entry receptor. This was confirmed by binding of soluble BTN2A1 to DC-SIGN-transfectants and its inhibition by a specific Ab. DC-SIGN bound to native BTN2A1 expressed on a range of tissues. However, BTN2A1 was not recognized on some normal cells such as HUVECs despite a similar expression level. The BTN2A1 of tumor cells such as HEK293T have more high-mannose moieties in comparison to HUVECs, and those high-mannose moieties are instrumental for binding to DC-SIGN. The data are consistent with tumor- or tissue-specific glycosylation of BTN2A1 governing recognition by DC-SIGN on immature monocyte-derived dendritic cells.

Previously, our studies identified nine genes and the chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease in individuals by genome-wide or candidate gene association studies. The present study examined the possible association of 13 polymorphisms at these 10 loci with the prevalence of type 2 diabetes mellitus (DM) in community-dwelling individuals. Study subjects comprised 6,027 individuals (797 subjects with type 2 DM and 5,230 controls) who were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender and body mass index (BMI) revealed that rs2116519 (C -> T) of FAM78B (P=0.0188), as well as rs2074379 (G -> A, P=0.0121) and rs2074388 (A -> G, P=0.0053) of ALPK1 were significantly (P<0.05) associated with the prevalence of type 2 DM. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for age, gender and BMI among all the individuals revealed that rs2116519, rs2074379 and rs2074388 were significantly associated with fasting plasma glucose level (P=0.0352, 0.0017 and 0.0010, respectively) and to blood glycosylated hemoglobin (hemoglobin A(1c)) content (P=0.0065, 0.0090 and 0.0079, respectively). Similar analysis among individuals not taking antidiabetic medication revealed that rs2074379 and rs2074388 were associated with the fasting plasma glucose level (P=0.0073 and 0.0042, respectively) and blood hemoglobin A(1c) content (P=0.0142 and 0.0126, respectively), whereas rs2116519 was associated with blood hemoglobin A(1c) content only (P=0.0470). ALPK1 may thus be a susceptibility gene for type 2 DM.