Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Del Besra

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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.


Publication metadata

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


Funding

Funder referenceFunder name
CA58896NCI NIH HHS
R01AI45889NIAID NIH HHS

Share