Characterization of a T Cell Receptor: Peptide/MHC Binding Interaction

To begin to examine the 2C TCR residues which provide a significant thermodynamic contribution toward the binding energy of a variety of ligands, including monoclonal antibodies (mAb), superantigens, and peptide/MHC ligands, we have expressed a family of 2C scTCRs which contain alanine point mutations in the complementarity determining regions (CDR) and fourth hypervariable region of the β chain. Using these mutant scTCRs, we have identified Vβ residues which are energetically important in the interaction of the 2C TCR with the anti-Vβ8 mAb F23.2, the anti-clonotypic mAb 1B2, and the peptide/MHC ligand QL9/L$\rm\sp{d}.$ Residues from all three CDRβ loops were implicated in the binding of the 2C TCR to QL9/L$\rm\sp{d}.$ Furthermore, every residue identified as part of the QL9/L$\rm\sp{d}$ epitope was also identified as part of the 1B2 epitope, suggesting that these two TCR ligands may share certain features in their tertiary structure even though their primary and secondary sequences are quite different. The construction of this panel of Vβ mutant scTCRs has also facilitated possible future identification of 2C TCR β chain residues which contact other peptide/MHC, mAb, and superantigen ligands.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Schlueter, Carol Joy

Contributors dc:contributor

• Kranz, David M.

• Health Sciences, Immunology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9737243

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84886