Critical role of glycosylation in determining the length and structure of T cell epitopes

Tamás G. Szabó, Robin Palotai, Péter Antal, Itay Tokatly, László Tóthfalusi, Ole Lund, György Nagy, András Falus, Edit I. Buzás

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Using a combined in silico approach, we investigated the glycosylation of T cell epitopes and autoantigens. The present systems biology analysis was made possible by currently available databases (representing full proteomes, known human T cell epitopes and autoantigens) as well as glycosylation prediction tools. Results. We analyzed the probable glycosylation of human T cell epitope sequences extracted from the ImmuneEpitope Database. Our analysis suggests that in contrast to full length SwissProt entries, only a minimal portion of experimentally verified T cell epitopes is potentially N- or O-glycosylated (2.26% and 1.22%, respectively). Bayesian analysis of entries extracted from the Autoantigen Database suggests a correlation between N-glycosylation and autoantigenicity. The analysis of random generated sequences shows that glycosylation probability is also affected by peptide length. Our data suggest that the lack of peptide glycosylation, a feature that probably favors effective recognition by T cells, might have resulted in a selective advantage for short peptides to become T cell epitopes. The length of T cell epitopes is at the intersection of curves determining specificity and glycosylation probability. Thus, the range of length of naturally occurring T cell epitopes may ensure the maximum specificity with the minimal glycosylation probability. Conclusion. The findings of this bioinformatical approach shed light on fundamental factors that might have shaped adaptive immunity during evolution. Our data suggest that amino acid sequence-based hypo/non- glycosylation of certain segments of proteins might be substantial for determining T cell immunity/autoimmunity.

Original languageEnglish
Article number4
JournalImmunome Research
Volume5
Issue number1
DOIs
StatePublished - 2009
Externally publishedYes

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