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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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
Issue number7
Publication statusPublished - Jul 1998


  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Computer Simulation
  • Crystallins
  • Epitopes
  • Female
  • Journal Article
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred Strains
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Receptors, Antigen, T-Cell
  • Research Support, Non-U.S. Gov't
  • Serine
  • T-Lymphocytes

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