The Tn Antigen—Structural Simplicity and Biological Complexity

Ju, Tongzhong; Otto, Vivianne I.; Cummings, Richard D.

Glycoproteins in animal cells contain a variety of glycan structures that are added co‐ and/or posttranslationally to proteins. Of over 20 different types of sugar–amino acid linkages known, the two major types are N‐glycans (Asn‐linked) and O‐glycans (Ser/Thr‐linked). An abnormal mucin‐type O‐glycan whose expression is associated with cancer and several human disorders is the Tn antigen. It has a relatively simple structure composed of N‐acetyl‐d‐galactosamine with a glycosidic α linkage to serine/threonine residues in glycoproteins (GalNAcα1‐O‐Ser/Thr), and was one of the first glycoconjugates to be chemically synthesized. The Tn antigen is normally modified by a specific galactosyltransferase (T‐synthase) in the Golgi apparatus of cells. Expression of active T‐synthase is uniquely dependent on the molecular chaperone Cosmc, which is encoded by a gene on the X chromosome. Expression of the Tn antigen can arise as a consequence of mutations in the genes for T‐synthase or Cosmc, or genes affecting other steps of O‐glycosylation pathways. Because of the association of the Tn antigen with disease, there is much interest in the development of Tn‐based vaccines and other therapeutic approaches based on Tn expression.