T cells discriminate between differentially phosphorylated forms of alphaB-crystallin, a major central nervous system myelin antigen

M J van Stipdonk, A A Willems, S Amor, C Persoon-Deen, P J Travers, C J Boog, J M van Noort

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Abstract

Factors such as developmental stage or physiological and infectious stress may change patterns of post-translational protein modification. In order to determine whether such regulated types of modification may influence T cell responsiveness to self proteins we examined the T cell response of SJL (H-2s) mice to alphaB-crystallin, a small heat shock protein that can exist in differentially phosphorylated forms. Epitope mapping revealed the presence of two T cell epitopes that are presented by I-As. One major epitope including residues 41-56 contains an amino acid residue (Ser45) that can be phosphorylated as the result of aging or stress. Accordingly, T cells from SJL mice discriminate between preparations of alphaB-crystallin that differ in their extent of phosphorylation at the level of whole protein as well as at the level of determinant-specific responses. Phosphorylation at Ser45 does not prevent binding of the peptide 41-56 to I-As and computer-assisted modelling of the peptide-MHC complex suggests that the phosphate group of the bound peptide extends outwards from the peptide-binding cleft and may thus be available for direct contact with TCR. Together, our data provide evidence that stress-inducible phosphorylation of alphaB-crystallin creates neo-determinants for T cells and, therefore, may contribute to the breakdown of peripheral tolerance to this self protein.

Original languageEnglish
Pages (from-to)943-50
Number of pages8
JournalInternational Immunology
Volume10
Issue number7
Publication statusPublished - Jul 1998

Cite this

van Stipdonk, M. J., Willems, A. A., Amor, S., Persoon-Deen, C., Travers, P. J., Boog, C. J., & van Noort, J. M. (1998). T cells discriminate between differentially phosphorylated forms of alphaB-crystallin, a major central nervous system myelin antigen. International Immunology, 10(7), 943-50.