Structural snapshot of aberrant antigen presentation linked to autoimmunity: The immunodominant epitope of MBP complexed with I-A^u

He, Xiao Lin, Radu, Caius, Sidney, John, Sette, Alessandro, Ward, E. Sally and Garcia, K. Christopher (2002) Structural snapshot of aberrant antigen presentation linked to autoimmunity: The immunodominant epitope of MBP complexed with I-A^u. Immunity, 17 (1), 83-94. (doi:10.1016/S1074-7613(02)00340-0).

Abstract

Murine experimental allergic encephalomyelitis (EAE) is a useful model for the demyelinating, autoimmune disease multiple sclerosis. In the EAE system, the immunodominant N-terminal epitope of myelin basic protein (MBP) is an unusually short, weakly binding peptide antigen which elicits highly biased TCR chain usage. In the 2.2 Å crystal structure of I-A^u/MBP1-11 complex, only MBP residues 1-7 are bound toward one end of the peptide binding cleft. The fourth residue of MBP1-11 is located in an incompatible p6 pocket of I-A^u, thus explaining the short half-life of I-A^u complexed with Ac1-11. MBP peptides extended at the C terminus of Ac1-11 result in dramatic affinity increases, likely attributed to register shifting to a higher affinity cryptic epitope, which could potentially mask the presentation of the immunodominant MBP1-11 peptide during thymic education.

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Contributors

Author: E. Sally Ward

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