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 language | English |
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Pages (from-to) | 943-50 |
Number of pages | 8 |
Journal | International Immunology |
Volume | 10 |
Issue number | 7 |
Publication status | Published - Jul 1998 |
Keywords
- 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