Polysaccharide processing and presentation by the MHCII pathway.
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.
Cobb
Brian A
BA
Channing Laboratory, Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Wang
Qun
Q
Tzianabos
Arthur O
AO
Kasper
Dennis L
DL
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D011134:Polysaccharides; D011948:Receptors, Antigen, T-Cell