T Cell Receptor Biochemistry, Repertoire Selection and General Features of TCR and Ig Structure

  1. Gregory R. Bock Organizer and
  2. Jamie A. Goode
  1. M. M. Davis1,2,
  2. D. S. Lyons2,
  3. J. D. Altman2,
  4. M. McHeyzer-Williams,
  5. J. Hampl1,
  6. J. J. Boniface2 and
  7. Y. Chien2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470515280.ch7

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

How to Cite

Davis, M. M., Lyons, D. S., Altman, J. D., McHeyzer-Williams, M., Hampl, J., Boniface, J. J. and Chien, Y. (2007) T Cell Receptor Biochemistry, Repertoire Selection and General Features of TCR and Ig Structure, in Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms (eds G. R. Bock and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470515280.ch7

Author Information

  1. 1

    Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305–5428, USA

  2. 2

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305–5428, USA

  1. Department of Immunology, Duke University Medical Center, Durham, NC 27707, USA.

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471965671

Online ISBN: 9780470515280

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Keywords:

  • tcell receptor biochemistry;
  • repertoire selection;
  • Ig structure;
  • peptide-MHC complex;
  • cytochrome c response

Summary

T cell recognition is a central event in the development of most immune responses, whether appropriate or inappropriate (i.e. autoimmune). We are interested in reducing T cell recognition to its most elemental components and relating this to biological outcome. In a model system involving a cytochrome c-specific I-Ek restricted T cell receptor (TCR) derived from the 2B4 hybridoma, we have studied the interaction of soluble TCR and soluble peptide–MHC complexes using surface plasmon resonance. We find a striking continuum in which biological activity correlates best with the dissociation rate of the TCR from the peptide–MHC complex. In particular, we have found that weak agonists have significantly faster off-rates than strong agonists and that antagonists have even faster off-rates. This suggests that the stability of TCR binding to a given ligand is critically important with respect to whether the T cell is stimulated, inhibited or remains indifferent. It also suggests that the phenomenon of peptide antagonists might be explained purely by kinetic models and that conformation, either inter- or intramolecular, may not be a factor. We have also studied TCR repertoire selection during the establishment of a cytochrome c response, initially using an anti-TCR antibody strategy, but more recently using peptide–MHC tetramers as antigen-specific staining reagents. These tetramers work well with either class I or class II MHC-specific TCRs and have many possible applications. Lastly, we have also tried to correlate the structural and genetic features of TCRs with their function. Recent data on TCR structure as well as previous findings with antibodies suggest that both molecules are highly dependent on CDR3 length and sequence variation to form specific contacts with antigens. This suggests a general ‘logic’ behind TCR and Ig genetics as it relates to structure and function that helps to explain certain anomalous findings and makes a number of clear predictions.