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 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 CDR3 beta 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 CDR3 beta 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.
Wienhold
W
W
Neuroimmunology Laboratory, Department of Neurology, University of Tübingen, 72076 Tübingen, Germany.
Malcherek
G
G
Jung
C
C
Stevanovic
S
S
Jung
G
G
Schild
H
H
Melms
A
A
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens / Q000502:physiology; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D013744:Tetanus Toxin