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Lookup NU author(s): Professor Del Besra
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alphabeta 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 alphabeta 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 beta-chain that were predicted to project between the CD1b alpha 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.
Author(s): Grant EP, Beckman EM, Behar SM, Degano M, Frederique D, Besra GS, Wilson IA, Porcelli SA, Furlong ST, Brenner MB
Publication type: Article
Publication status: Published
Journal: Journal of Immunology
Year: 2002
Volume: 168
Issue: 8
Pages: 3933-3940
ISSN (print): 0022-1767
ISSN (electronic): 1550-6606
Publisher: American Association of Immunologists
