Definition and transfer of a serological epitope specific for peptide-empty forms of MHC class I

Yik Y.L. Yu, Nancy B. Myers, Christine M. Hilbert, Michael R. Harris, Ganesaratnam K. Balendiran, Ted H. Hansen

Research output: Contribution to journalArticle

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Abstract

Nascent class I molecules have been hypothesized to undergo a conformational change when they bind peptide based on the observation that most available antibodies only detect peptide-loaded class I. Furthermore recent evidence suggests that this peptide-facilitated conformational change induces the release of class I from association with transporter associated with antigen processing (TAP)/tapasin and other endoplasmic reticulum proteins facilitating class I assembly. To learn more about the structure of peptide-empty class I, we have studied mAb 64-3-7 that is specific for peptide-empty forms of L(d). We show here that mAb 64-3-7 detects a linear stretch of amino acids including principally residues 48Q and 50P. Furthermore, we demonstrate that the 64-3-7 epitope can be transferred to other class I molecules with limited mutagenesis. Interestingly, in the folded class I molecule residues 48 and 50 are on a loop connecting a β strand (under the bound peptide) with the α1 helix (rising above the ligand binding site). Thus it is attractive to propose that this loop is a hinge region. Importantly, the three-dimensional structure of this loop is strikingly conserved among class I molecules. Thus our findings suggest that all class I molecules undergo a similar conformational change in the loop around residues 48 and 50 when they associate with peptide.

Original languageEnglish
Pages (from-to)1897-1905
Number of pages9
JournalInternational Immunology
Volume11
Issue number12
StatePublished - Dec 1 1999

Keywords

  • H chain conformation
  • Peptide binding

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    Yu, Y. Y. L., Myers, N. B., Hilbert, C. M., Harris, M. R., Balendiran, G. K., & Hansen, T. H. (1999). Definition and transfer of a serological epitope specific for peptide-empty forms of MHC class I. International Immunology, 11(12), 1897-1905.