Binding of peptides lacking consensus anchor residue alters H-2L(d) serologic recognition

J. C. Solheim, B. M. Carreno, J. D. Smith, J. Gorka, N. B. Myers, Z. Wen, J. M. Martinko, D. R. Lee, T. H. Hansen

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58 Scopus citations

Abstract

CTL recognize class I MHC/peptide complexes on the surface of target cells. Crystallographic and serologic data have indicated that peptide ligands can influence the conformation of class I molecules and hence T cell recognition. How the binding of peptides with disparate sequence motifs affects the conformation of distinct regions within a class I molecule remains unknown. A series of site-directed mutants of the murine class I molecule H-2L(d) was studied to address this question. These mutants were generated by in vitro mutagenesis and used to map the serologic epitopes recognized by a panel of L(d)-reactive mAb. The influence of six different ligands on serologic recognition by these mAb was then examined. Of 12 mAb tested, only one, B22/249, was found to be significantly influenced by the bound peptide. Peptide discrimination by B22/249 was observed at the cell surface and in immunoprecipitates of L(d) after incubation with two of the six ligands. The two peptides that caused suboptimal B22/249 recognition of L(d)/peptide lack a proline at position 2, which is present in the other four peptides and has previously been defined as an anchor residue for L(d) ligands. The epitope on L(d) detected by mAb B22/249 includes residues 63 to 70 on the α1 domain helix. Two of these residues are in pocket B, which computer modeling predicts to be in contact with the second residue of L(d)- binding peptides. Therefore, these data imply that a mAb to a class I molecule can distinguish peptides with different motifs, possibly reflecting peptide-dependent conformational changes in the class I molecule.

Original languageEnglish (US)
Pages (from-to)5387-5397
Number of pages11
JournalJournal of Immunology
Volume151
Issue number10
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Solheim, J. C., Carreno, B. M., Smith, J. D., Gorka, J., Myers, N. B., Wen, Z., Martinko, J. M., Lee, D. R., & Hansen, T. H. (1993). Binding of peptides lacking consensus anchor residue alters H-2L(d) serologic recognition. Journal of Immunology, 151(10), 5387-5397.