Immunoglobulins are the major secretory products of the adaptive immune system. Each is characterized by a distinctive set of glycoforms that reflects the wide variation in the number, type, and location of their oligosaccharides. In a given physiological state, glycoform populations are reproducible; therefore, disease-associated alterations provide diagnostic biomarkers (e.g., for rheumatoid arthritis) and contribute to disease pathogenesis. The oligosaccharides provide important recognition epitopes that engage with lectins, endowing the immunoglobulins with an expanded functional repertoire. The sugars play specific structural roles, maintaining and modulating effector functions that are physiologically relevant and can be manipulated to optimize the properties of therapeutic antibodies. New molecular models of all the immunoglobulins are included to provide a basis for informed and critical discussion. The models were constructed by combining glycan sequencing data with oligosaccharide linkage and dynamics information from the Glycobiology Institute experimental database and protein structural data from “The Protein Data Bank.”

Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were also seen in a 16-residue segment. On extraction, the islet amyloid is particulate and insoluble like the core particles of Alzheimer disease. Their monomers have similar molecular masses, each having a hydropathic region that can probably form beta-pleated sheets. The accumulation of amyloid, including diabetes-associated peptide, in islets may impair islet function in type 2 diabetes mellitus.