Fine specificity of TCR complementarity-determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1-lipid complex

Ethan P. Grant, Evan M. Beckman, Samuel M. Behar, Massimo Degano, Daphney Frederique, Gurdyal S. Besra, Ian A. Wilson, Steven A. Porcelli, Stephen T. Furlong, Michael B. Brenner

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

αβ TCR can recognize peptides presented by MHC molecules or lipids and glycolipids presented by CD1 proteins. Whereas the structural basis for peptide/MHC recognition is now clearly understood, it is not known how the TCR can interact with such disparate molecules as lipids. Recently, we demonstrated that the αβ TCR confers specificity for both the lipid Ag and CD1 isoform restriction, indicating that the TCR is likely to recognize a lipid/CD1 complex. We hypothesized that lipids may bind to CD1 via their hydrophobic alkyl and acyl chains, exposing the hydrophilic sugar, phosphate, and other polar functions for interaction with the TCR complementarity-determining regions (CDRs). To test this model, we mutated the residues in the CDR3 region of the DN1 TCR β-chain that were predicted to project between the CD1b α helixes in a model of the TCR/CD1 complex. In addition, we tested the requirement for the negatively charged and polar functions of mycolic acid for Ag recognition. Our findings indicate that the CDR loops of the TCR form the Ag recognition domain of CD1-restricted TCRs and suggest that the hydrophilic domains of a lipid Ag can form a combinatorial epitope recognized by the TCR.

Original languageEnglish (US)
Pages (from-to)3933-3940
Number of pages8
JournalJournal of Immunology
Volume168
Issue number8
DOIs
StatePublished - Apr 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Grant, E. P., Beckman, E. M., Behar, S. M., Degano, M., Frederique, D., Besra, G. S., Wilson, I. A., Porcelli, S. A., Furlong, S. T., & Brenner, M. B. (2002). Fine specificity of TCR complementarity-determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1-lipid complex. Journal of Immunology, 168(8), 3933-3940. https://doi.org/10.4049/jimmunol.168.8.3933