Benzylamine oxidase : an enzyme in search of a function

Imperial Users onl

Prophet In His Own Country: Carlos Chagas And The Nobel Prize.

In 1909, Carlos Chagas (1878-1934) discovered a new protozoon, Trypanosoma cruzi, and the (previously unknown) disease that it causes. Within a few months, virtually single-handed, he described the pathogen, its vector, and the clinical features of American trypanosomiasis (Chagas disease), a feat unique in medical history. He headed the Oswaldo Cruz Institute after the death of its founder (1917) until his own death; and from 1920 until 1926 he also directed the Brazilian Department of Public Health. His discovery brought him worldwide acclaim, but at home antagonism against Chagas, muted for years, finally flared up in a campaign that was acted out in the 1921-22 plenary sessions of the National Academy of Medicine. Chagas's name was repeatedly proposed for the Nobel Prize but he never received it; this hostile campaign may have been instrumental in costing him the award.46453254

Endogenous human cytomegalovirus gB is efficiently presented by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB--expressed by adenovirus vectors or after HCMV infection--and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells