Polysaccharide Processing and Presentation by the MHCII Pathway

• Published in: Cell Vol. 117; no. 5; pp. 677 - 687
• Main Authors: Cobb, Brian A, Wang, Qun, Tzianabos, Arthur O, Kasper, Dennis L
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 28-05-2004
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2004.05.001

The adaptive immune system functions through the combined action of antigen-presenting cells (APCs) and T cells. Specifically, class I major histocompatibility complex antigen presentation to CD8
+ T cells is limited to proteosome-generated peptides from intracellular pathogens while the class II (MHCII) endocytic pathway presents only proteolytic peptides from extracellular pathogens to CD4
+ T cells. Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria can activate CD4
+ T cells. Here we show that ZPSs are processed to low molecular weight carbohydrates by a nitric oxide-mediated mechanism and presented to T cells through the MHCII endocytic pathway. Furthermore, these carbohydrates bind to MHCII inside APCs for presentation to T cells. Our observations begin to elucidate the mechanisms by which some carbohydrates induce important immunologic responses through T cell activation, suggesting a fundamental shift in the MHCII presentation paradigm.