T cells discriminate between differentially phosphorylated forms of αB-crystallin, a major central nervous system myelin antigen
article
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-2(S)) mice to αB-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-A(S). 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 αB-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-A(S) 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 αB-crystallin creates neo-determinants for T cells and, therefore, may contribute to the breakdown of peripheral tolerance to this self protein.
Topics
αB-crystallinEpitope analysisHeal shock proteinI-A(s) binding motifPhosphorylationPost-translational modificationTCRAmino Acid SequenceAnimalsBinding SitesCattleComputer SimulationCrystallinsEpitopesFemaleLymphocyte ActivationMiceMice, Inbred StrainsModels, MolecularMolecular Sequence DataPhosphorylationReceptors, Antigen, T-CellSerineT-Lymphocytes
TNO Identifier
234546
ISSN
09538178
Source
International Immunology, 10(7), pp. 943-950.
Pages
943-950
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