title: Antibody responses to glycolipid-borne carbohydrates require CD4+ T cells but not CD1 or NKT cells.
abstract: Naturally occurring anti-carbohydrate antibodies play a major role in both the innate and adaptive immune responses. To elicit an anti-carbohydrate immune response, glycoproteins can be processed to glycopeptides and presented by the classical antigen-presenting molecules, major histocompatibility complex (MHC) Class I and II. In contrast, much less is known about the mechanism(s) for anti-carbohydrate responses to glycolipids, although it is generally considered that the CD1 family of cell surface proteins presents glycolipids to T cells or natural killer T (NKT) cells. Using model carbohydrate systems (isogloboside 3 and B blood group antigen), we examined the anti-carbohydrate response on glycolipids using both antibody neutralisation and knockout mouse-based experiments. These studies showed that CD4(+) T cells were required to generate antibodies to the carbohydrates expressed on glycolipids, and unexpectedly, these antibody responses were CD1d and NKT cell independent. They also did not require peptide help. These data provide new insight into glycolipid antigen recognition by the immune system and indicate the existence of a previously unrecognised population of glycolipid antigen-specific, CD1-independent, CD4(+) T cells.
authors.affiliation: Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia.
authors.forename: Dale
authors.initials: D
authors.lastname: Christiansen
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Vaughan
authors.forename: Julie
authors.initials: J
authors.lastname: Milland
authors.forename: Julie
authors.initials: J
authors.lastname: Miland
authors.forename: Natalie
authors.initials: N
authors.lastname: Dodge
authors.forename: Effie
authors.initials: E
authors.lastname: Mouhtouris
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Sandrin
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D011817:Rabbits
chemical_list: D055610:Antigens, CD1d; D006017:Glycolipids