Peptide-induced rescue of serologic epitopes on class I MHC molecules

J. C. Solheim, B. M. Carreno, N. B. Myers, D. R. Lee, T. H. Hansen

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

To monitor conformational changes in MHC class I structure induced by interaction with peptide or β2-microglobulin (β2-m), we have taken a serologic approach. Previous studies by us and others have defined circumstances wherein specific peptides can decrease serologic recognition of class I molecules. However, such blocking of serologic epitopes has often been interpreted as steric hindrance by peptide side chains. In this paper, we describe peptide-induced gains in recognition by mAbs 30-5-7, 34-1-2, and B22/249. In experiments with mAb 30-5-7, impaired reactivity, which resulted from an L(d) loop mutation, was specifically rescued by the binding of a β- galactosidase-derived peptide to the L(d) mutant. In studies with mAb 34-1- 2, poor L(d) detection was enhanced by mutations in L(d) at β2-m interaction sites or by changes within the peptide-binding groove. To evaluate whether known peptides in the L(d) groove could influence 34-1-2 recognition, we tested six peptide ligands, four of which increased the reactivity of 34-1-2 with the L(d)-expressing cell to various degrees (up to 14-fold). It is of interest that L(d) mutations at position 9 and 95/97 made significant differences in the ranking of the peptides in regard to their ability to increase recognition by 34-1-2 and B22/249. This finding suggests that mutations in the binding groove can alter peptide conformation and result in secondary changes in class I structure. On the basis of the cumulative serologic data, we propose that the class I molecule displays considerable fluidity, and is structurally influenced by both β2-m and peptide.

Original languageEnglish (US)
Pages (from-to)1188-1197
Number of pages10
JournalJournal of Immunology
Volume154
Issue number3
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Solheim, J. C., Carreno, B. M., Myers, N. B., Lee, D. R., & Hansen, T. H. (1995). Peptide-induced rescue of serologic epitopes on class I MHC molecules. Journal of Immunology, 154(3), 1188-1197.