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How TCRs bind MHCs, peptides, and coreceptors.
Markus G Rudolph1, Robyn L Stanfield, Ian A Wilson
1Department of Molecular Structural Biology, University of Göttingen, 37077 Göttingen, Germany. mrudolp2@gwdg.de
Annual Review of Immunology
|March 23, 2006
Summary
Structural studies reveal diverse T cell receptor (TCR) antigen recognition modes. Despite extensive data on TCR/pMHC complexes, the basis for MHC restriction and signaling remains unclear, highlighting varied antigen binding strategies.
Area of Science:
- Immunology
- Structural Biology
- Biochemistry
Background:
- Over 24 class I and class II T cell receptor (TCR)/MHC-peptide (pMHC) complexes have been structurally characterized since 1996.
- Structural data now encompasses alphabeta TCRs, gammadelta TCRs, and accessory molecules like CD4, CD8, and CD3 components.
- This growing structural database reveals significant variability in TCR/pMHC recognition.
Purpose of the Study:
- To compare antigen recognition mechanisms between alphabeta and gammadelta T cells using structural data.
- To advance the structural understanding of the T cell receptor signaling complex.
- To investigate the structural basis of MHC restriction and T cell signaling.
Main Methods:
- X-ray crystallography was used to determine the structures of TCR/pMHC complexes.
- Comparative structural analysis of free and bound TCRs, including gammadelta TCRs.
- Integration of structural data for TCRs, accessory molecules, and coreceptors.
Main Results:
- A substantial degree of structural variability in TCR/pMHC recognition has been defined.
- Comparisons between alphabeta and gammadelta TCR structures highlight different antigen recognition modes.
- Structural insights into TCR accessory and coreceptor molecules have been gained.
Conclusions:
- Despite extensive structural data, a common binding mode or signaling mechanism for TCR/pMHC complexes has not been identified.
- The structural basis for MHC restriction and signaling remains elusive.
- Existing structures demonstrate the diverse strategies employed by TCRs to recognize a wide array of antigens.