An example of immunodominance: engagement of synonymous TCR by invariant CDR3 beta

The structural basis of the T cell response against immunodominant tetanus toxin (TT)-derived peptides was investigated using TT-specific T cell clone s raised from a DRB1*0301 homozygous donor. Three peptides forming T cell e pitopes were identified, including one, TT(1272-1284), that stimulated four different TT-specific T cell clones. TCR sequence analysis revealed that t hese synonymous TCR shared only arginine at the third position of the CDR3 beta loop, This prominent residue may form a salt bridge with a correspondi ng aspartate at the relative position 8 (P8) of the antigenic peptide TT(12 72-1284) as suggested from amino acid replacement analysis. A similar scena rio was observed for a second TT epitope, TT(279-296), and its correspondin g TCR, These examples show that immunodominance may result from a single st rong amino acid interaction between TCR CDR3 beta loops here in contact wit h the C-terminus of the antigenic peptide. Such a dominant interaction coul d 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.