International Immunology, Vol. 12, No. 6, 747-756,
June 2000
© 2000 Japanese Society for Immunology
An example of immunodominance: engagement of synonymous TCR by invariant CDR3ß
Neuroimmunology Laboratory, Department of Neurology,
1 Institute for Cell Biology, Department of Immunology and
2 Institute of Organic Chemistry, University of Tübingen, 72076 Tübingen, Germany
3 Immunology Division, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
Correspondence to: W. Wienhold
The structural basis of the T cell response against immunodominant tetanus toxin (TT)-derived peptides was investigated using TT-specific T cell clones raised from a DRB1*0301 homozygous donor. Three peptides forming T cell epitopes were identified, including one, TT(1272–1284), that stimulated four different TT-specific T cell clones. TCR sequence analysis revealed that these synonymous TCR shared only arginine at the third position of the CDR3ß loop. This prominent residue may form a salt bridge with a corresponding aspartate at the relative position 8 (P8) of the antigenic peptide TT(1272–1284) as suggested from amino acid replacement analysis. A similar scenario was observed for a second TT epitope, TT(279–296), and its corresponding TCR. These examples show that immunodominance may result from a single strong amino acid interaction between TCR CDR3ß loops here in contact with the C-terminus of the antigenic peptide. Such a dominant interaction could compensate for weaker contacts between other residues of the TCR and the antigenic peptide, and would allow the recognition of a single peptide–MHC complex by a broader synonymous TCR repertoire and could thus contribute to its immunodominance.
Keywords: DRB1*0301, peptide binding, salt bridge, T cell epitopes, T cell repertoire, TCR contact residues
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