|
|
|
|
|
|
|
||
Articles |
Department of Molecular Biology and Skaggs Institute of Chemical Biology, Scripps Research Institute, La Jolla, California 92037; and the Division of Dermatology, University of California Los Angeles School of Medicine, Los Angeles, California 90095
The T cell antigen receptor (TCR) mediates recognition of peptide antigens bound in the groove of major histocompatibility complex (MHC) molecules. This dual recognition is mediated by the complementarity-determining residue (CDR) loops of the
and β chains of a single TCR which contact exposed residues of the peptide antigen and amino acids along the MHC helices. The recent description of T cells that recognize hydrophobic microbial lipid antigens has challenged immunologists to explain, in molecular terms, the nature of this interaction. Structural studies on the murine CD1d1 molecule revealed an electrostatically neutral putative antigen-binding groove beneath the CD1 helices. Here, we demonstrate that /β TCRs, when transferred into TCR-deficient recipient cells, confer specificity for both the foreign lipid antigen and CD1 isoform. Sequence analysis of a panel of CD1-restricted, lipid-specific TCRs reveals the incorporation of template-independent N nucleotides that encode diverse sequences and frequent charged basic residues at the V(D)J junctions. These sequences permit a model for recognition in which the TCR CDR3 loops containing charged residues project between the CD1 helices, contacting the lipid antigen hydrophilic head moieties as well as adjacent CD1 residues in a manner that explains antigen specificity and CD1 restriction.
Key Words: CD1 • antigen presentation • T cell receptor • Mycobacterium tuberculosis • mycolic acid
Abbreviations used: CDR, complementarity-determining residues; rhIL-2, recombinant human IL-2; UTR, untranslated region.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| TABLE OF CONTENTS |
|
