Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Associated disease: infection due to Streptococcus pneumoniae [ICD11:
XN3PW 
]
NCBI PubMed ID: 30510007Publication DOI: 10.1073/pnas.1816401115Journal NLM ID: 7505876Publisher: National Academy of Sciences
Correspondence: D.L. Kasper <dennis_kasper
hms.harvard.edu>
Institutions: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, Department of Chemistry, University of Milan, 20133 Milan, Italy, Technical R&D, GSK Vaccines, 53100 Siena, Italy
Glycoconjugate vaccines are among the most effective interventions for preventing several serious infectious diseases. Covalent linkage of the bacterial capsular polysaccharide to a carrier protein provides CD4+ T cells with epitopes that facilitate a memory response to the polysaccharide. Classically, the mechanism responsible for antigen processing was thought to be similar to what was known for hapten-carrier conjugates: protease digestion of the carrier protein in the endosome and presentation of a resulting peptide to the T cell receptor on classical peptide-recognizing CD4+ T cells. Recently, an alternative mechanism has been shown to be responsible for the memory response to some glycoconjugates. Processing of both the protein and the polysaccharide creates glycopeptides in the endosome of antigen-presenting cells. For presentation, the peptide portion of the glycopeptide is bound to MHCII, allowing the covalently linked glycan to activate carbohydrate-specific helper CD4+ T cells (Tcarbs). Herein, we assessed whether this same mechanism applies to conjugates prepared from other capsular polysaccharides. All of the glycoconjugates tested induced Tcarb-dependent responses except that made with group C Neisseria meningitidis; in the latter case, only peptides generated from the carrier protein were critical for helper T cell recognition. Digestion of this acid-sensitive polysaccharide, a linear homopolymer of α(2 → 9)-linked sialic acid, to the size of the monomeric unit resulted in a dominant CD4+ T cell response to peptides in the context of MHCII. Our results show that different mechanisms of presentation, based on the structure of the carbohydrate, are operative in response to different glycoconjugate vaccines.
vaccine, glycoconjugate, Tcarb, antigen presentation, group C Neisseria meningitidis
Structure type: polymer chemical repeating unit
Location inside paper: table S1, p.13 Pneumo conjugates
Aglycon: carrier protein OVA,KLH
Compound class: CPS
Contained glycoepitopes: IEDB_115136,IEDB_140630,IEDB_142488,IEDB_146664,IEDB_149553,IEDB_423153,IEDB_983931,SB_192
Methods: ELISA, biological assays, serological methods, HPSEC, statistical analysis, immunization, conjugation, flow cytometry analysis, antigen presentation by BMDCs
Related record ID(s): 2688, 2689, 2690, 2691, 2692
NCBI Taxonomy refs (TaxIDs): 1313Reference(s) to other database(s): GTC:G48944PP
Show glycosyltransferases
There is only one chemically distinct structure:
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