Immunity 2002 Jul;17(1):83-94
He X, Radu C, Sidney J, Sette A, Ward ES, Garcia KC.
Department of Microbiology and Immunology, Stanford University School of Medicine, 94305, Stanford, CA, USA
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 A 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.