Radically altered T cell receptor signaling in glycopeptide-specific T cell hybridoma induced by antigen with minimal differences in the glycan group
✍ Scribed by Teis Jensen; Mette Nielsen; Monika Gad; Peter Hansen; Shiro Komba; Morten Meldal; Niels Ødum; Ole Werdelin
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 388 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
A T cell hybridoma raised against the synthetic glycopeptide T 72 (Tn) was used to study whether the initial TCR signaling events are markedly different when the hybridoma is stimulated with glycopeptides closely related to the cognate glycopeptide antigen. T 72 (Tn) has an § -D-GalNAc group O-linked to the central threonine in the decapeptide VITAFTEGLK, and the hybridoma is known to be highly specific for this carbohydrate group. T 72 (Tn)-pulsed APC induced tyrosine phosphorylation of the TCR-´21and 23-kDa proteins and the downstream p42/44 MAP kinase and strong IL-2 secretion. APC pulsed with T 72 ( § -D-GlcNAc), which differs from T 72 (Tn) solely by the orientation of a hydroxy group in the carbohydrate structure, completely failed to induce detectable tyrosine phosphorylation and IL-2 secretion. APC pulsed with S 72 (Tn), which differs from T 72 (Tn) by not having a methyl group in the serine amino acid side chain to which the glycan is attached, induced partial tyrosine phosphorylation of the TCR-´21-kDa protein, no tyrosine phosphorylation of the MAP kinases and no IL-2 production. Molecular modeling of the MHC/glycopeptide complex revealed that the dramatic difference between the stimulatory power of T 72 (Tn) and T 72 ( § -D-GlcNAc) is mainly due to very small differences in the TCR exposed carbohydrate structure.