Alternative peptide binding motifs of Qa-2 class Ib molecules define rules for binding of self and nonself peptides

Piotr Tabaczewski, Eugene Chiang, Maile Henson, Iwona Stroynowski

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Studies of naturally processed peptides eluted from membrane-bound and soluble isoforms of murine class Ib Qa-2 molecules determined several features of these ligands, such as the conserved nonameric length and the preferred usage of specific residues at four to six of nine peptide positions. The structural information derived from these studies proved insufficient to distinguish between two interpretations: 1) that Qa-2 are peptide receptors of higher stringency than ordinary class I molecules, and 2) that Qa-2 molecules, like classical class I Ags, bind diverse arrays of peptides. We have addressed this issue by a systematic analysis of peptide residues involved in the binding of membrane-bound Qa-2 molecule, MQ9b. The optimal binding of synthetic peptides in vitro occurs at neutral pH. Two dominant anchors are required for peptide binding to MQ9b: His at position 7 and a hydrophobic residue, Leu, Ile, or Phe, at position 9. In addition, one or two auxiliary anchors participate in binding. The identity and the position of the auxiliary anchors differ from peptide to peptide, suggesting that the binding motifs defined from pool sequencing are composed of many superimposed alternative motifs present in individual peptides. The number of anchors used by Qa-2 peptides is similar to that found in ligands of classical class I Ags. Consequently, the Qa-2 are predicted to bind large repertoires of self and nonself peptides. In support of this interpretation we demonstrate that MQ9b binds strongly 5 of 17 motif-positive, pathogen-derived synthetic peptides.

Original languageEnglish (US)
Pages (from-to)2771-2781
Number of pages11
JournalJournal of Immunology
Volume159
Issue number6
StatePublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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