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

Xiao Lin He, Caius Radu, John Sidney, Alessandro Sette, E. Sally Ward, K. Christopher Garcia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalImmunity
Volume17
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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