Peptide-induced conformational changes in class I molecules: Direct detection by flow cytometry

Eric M. Rohren, Daniel J. McCormick, Larry R. Pease

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Activation of a T cell in response to peptide bound to class I MHC occurs by the sum of interactions across the area of contact between the TCR, the peptide, and class I MHC. It has been observed recently that substitution of the peptide residue at a position that is not accessible from the exterior of the class I molecule modulates T cell responses, raising the possibility that there may be indirect structural effects in the peptide-class I complex as a consequence of peptide binding. This report describes the use of mAbs to probe the conformation of the α1 and α2 domains of the mouse class I molecule Kb when bound to ovalbumin peptide and a panel of 19 peptide analogues that differ at position 2 (P2). By crystallographic data, side chains of this position are buried in the Ag binding cleft and have no direct access to the TCR. Substitution of position 2 results in a measurable change in conformation of the class I molecule, a change that correlates with the ability to stimulate T cells. This leads to a model that T cell activation by the peptide-class I complex may occur in three ways: 1) direct interaction of the TCR with the class I heavy chain, 2) direct interaction of the TCR with solvent-accessible peptide side chains, and 3) indirect interaction of peptide with TCR mediated via conformational perturbations in the class I complex.

Original languageEnglish (US)
Pages (from-to)5337-5343
Number of pages7
JournalJournal of Immunology
Issue number11
StatePublished - Jun 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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