[HTML][HTML] Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au

X He, C Radu, J Sidney, A Sette, ES Ward, KC Garcia - Immunity, 2002 - cell.com
Immunity, 2002cell.com
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 IA 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 …
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-Au/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-Au, thus explaining the short half-life of I-Au 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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