Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes

Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7445-50. doi: 10.1073/pnas.96.13.7445.

Abstract

Class II MHC molecules are known to exist in conformational variants. "Floppy" and "compact" forms of murine MHC molecules, for example, are discriminated by their migration behavior on SDS/PAGE and represent empty and ligand-loaded forms. Here we show that formation of distinctly faster-migrating ligand complexes (F-forms) rather than the normal compact (C-) forms of HLA-DR1 or -DR4 results from extensions of minimal peptide epitopes (such as HA306-318 or IC106-120) by approximately 10 amino acids at either the N or the C terminus. Two similar but distinct F-forms (FI and FII) were detected, depending on the site of the extension. Both F-forms were characterized by increased surface hydrophobicity and reduced SDS-stability. Native gel separations and size exclusion chromatography indicated that the F-forms had increased hydrodynamic radii compared with the C-form and an apparent size similar to that of empty MHC molecules. The regions on the ligand overhangs responsible for the effect began at a distance of approximately 5 amino acids on either side of the epitopes, comprised 4-8 amino acids (i.e., a total overhang of 9-14), and did not have a particular sequence preference. The possible functional significance of these forms is discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation*
  • Epitopes / chemistry
  • Epitopes / immunology
  • HLA-D Antigens / chemistry*
  • HLA-D Antigens / immunology
  • Humans
  • Ligands
  • Peptides / chemistry*
  • Peptides / immunology
  • Protein Conformation*
  • Structure-Activity Relationship

Substances

  • Epitopes
  • HLA-D Antigens
  • Ligands
  • Peptides