Title
A Molecular Basis for How a Single TCR Interfaces Multiple Ligands
Document Type
Article
Publication Date
1998
Abstract
CD8+ T cells respond to Ags when their clonotypic receptor, the TCR, recognizes nonself peptides displayed by MHC class I molecules. The TCR/ligand interactions are degenerate because, in its life time, the TCR interacts with self MHC class I-self peptide complexes during ontogeny and with self class I complexed with nonself peptides to initiate Ag-specific responses. Additionally, the same TCR has the potential to interact with nonself class. I complexed with nonself peptides. How a single TCR interfaces multiple ligands remains unclear. Combinatorial synthetic peptide libraries provide a powerful tool to elucidate the rules that dictate how a single TCR engages multiple ligands. Such libraries were used to probe the requirements for TCR recognition by cloned CD8+ T cells directed against Ags presented by H-2Kb class I molecules. When H-2Kb contact residues were examined, position 3 of the peptides proved more critical than the dominant carboxyl- terminal anchor residue. Thus, secondary anchor residues can play a dominant role in determining the antigenicity of the epitope presented by class I molecules. When the four solvent-exposed potential TCR contact residues were examined, only one or two of these positions required structurally similar residues. Considerable structural variability was tolerated at the remaining two or three solvent-exposed residues of the Kb-binding peptides. The TCR, therefore, requires close physico-chemical complementarity with only a few amino acid residues, thus explaining why TCR/MHC interactions are of low affinity and degenerate.
Recommended Citation
Boesteanu, A.; Brehm, M.; Mylin, Larry M.; Christianson, G. J.; Tevethia, S. S.; Roopenian, D. C.; and Joyce, S., "A Molecular Basis for How a Single TCR Interfaces Multiple Ligands" (1998). Biology Educator Scholarship. 104.
https://mosaic.messiah.edu/bio_ed/104
Comments
Boesteanu, A., Brehm, M., Mylin, L. M., Christianson, G. J., Tevethia, S. S., Roopenian, D. C., & Joyce, S. (1998). A molecular basis for how a single TCR interfaces multiple ligands. Journal of immunology (Baltimore, Md. : 1950), 161(9), 4719–4727.