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

• Published in: International immunology 1998, Vol.10 (7), p.943-950
• Main Authors: Van Stipdonk, MJB, Willems, A A, Amor, S, Persoon-Deen, C, Travers, P J, Boog, CJP, Van Noort, JM
• Format: Article
• Language: English
• ISSN: 0953-8178
• DOI: 10.1093/intimm/10.7.943

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 super(s)) mice to alpha B-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 super(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 alpha B-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 super(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 alpha B-crystallin creates neo-determinants for T cells and, therefore, may contribute to the breakdown of peripheral tolerance to this self protein.