Roles of mucin-type O-glycans synthesized by core2beta1,6-N-acetylglucosaminyltransferase.

Core 2 branched O-linked oligosaccharides (O-glycans) represent the first example of onco-developmental antigens in mucin-type O-glycans. Core 2 branched O-glycans are expressed in immature T lymphocytes (cortical thymocytes), disappear on mature T lymphocytes (medullary thymocytes) and T lymphocytes in the peripheral blood, and appear again in activated T lymphocytes, leukemic cells, and other cancer cells. Core 2 branched O-linked oligosaccharides are synthesized by Core2beta1,6-N-acetylglucosaminyltransferase (Core2GlcNAcT). The first cloned Core2GlcNAcT-1 has been inactivated in mice through homologous recombination, and mutants show significantly reduced leukocyte rolling on E-, P-, and L-selectin-coated plates. Moreover, mutant mice exhibit an impaired peritoneal inflammatory response associated with reduced neutrophil infusion. By contrast, lymphocyte homing to secondary lymphoid organs is only marginally compromised. These results combined indicate that Core2GlcNAcT-1 plays a major role in leukocyte trafficking and distinguish leukocyte trafficking to inflamed sites from lymphocyte homing to secondary lymphoid organs.