Molecular recognition of human CD1b antigen complexes: Evidence for a common pattern of interaction with αβ TCRs

A. Melian, G. F.M. Watts, A. Shamshiev, G. De Libero, A. Clatworthy, M. Vincent, M. B. Brenner, S. Behar, K. Niazi, R. L. Modlin, S. Almo, D. Ostrov, S. G. Nathenson, S. A. Porcelli

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Ag-specific T cell recognition is mediated through direct interaction of clonotypic TCRs with complexes formed between Ag-presenting molecules and their bound ligands. Although characterized in substantial detail for class I and class II MHC encoded molecules, the molecular interactions responsible for TCR recognition of the CD1 lipid and glycolipid Ag-presenting molecules are not yet well understood. Using a panel of epitope-specific Abs and site-specific mutants of the CD1b molecule, we showed that TCR interactions occur on the membrane distal aspects of the CD1b molecule over the α1 and α2 domain helices. The location of residues on CD1b important for this interaction suggested that TCRs bind in a diagonal orientation relative to the longitudinal axes of the α helices. The data point to a model in which TCR interaction extends over the opening of the putative Ag-binding groove, making multiple direct contacts with both α helices and bound Ag. Although reminicent of TCR interaction with MHC class I, our data also pointed to significant differences between the TCR interactions with CD1 and MHC encoded Ag-presenting molecules, indicating that Ag receptor binding must be modified to accommodate the unique molecular structure of the CD1b molecule and the unusual Ags it presents.

Original languageEnglish (US)
Pages (from-to)4494-4504
Number of pages11
JournalJournal of Immunology
Volume165
Issue number8
DOIs
StatePublished - Oct 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Melian, A., Watts, G. F. M., Shamshiev, A., De Libero, G., Clatworthy, A., Vincent, M., Brenner, M. B., Behar, S., Niazi, K., Modlin, R. L., Almo, S., Ostrov, D., Nathenson, S. G., & Porcelli, S. A. (2000). Molecular recognition of human CD1b antigen complexes: Evidence for a common pattern of interaction with αβ TCRs. Journal of Immunology, 165(8), 4494-4504. https://doi.org/10.4049/jimmunol.165.8.4494