Structure, Function and Engineering of Peptide -Mhc Binding Receptors

In chapter 5, a T cell receptor interaction with its peptide-MHC ligand was explored using various TCR mutants engineered by yeast display. Previous work in the lab showed that mutations in the CDR3 regions of the TCR could generate higher-affinity, peptide-specific TCR variants. In contrast, other CDRs (CDR1, and especially CDR2) of the TCR are typically located over the MHC helices and thus may not be positioned to interact directly with peptide. Mutations in these CDRs might be expected to yield high-affinity but reduced peptide specificity (i.e. interactions with MHC determinants). Surprisingly, mutants in CDR1 and CDR2 retained peptide specificity, suggesting that even TCR regions that are not directly in contact with the peptide can influence peptide specificity. Furthermore, random mutagenesis of the TCR revealed that single-site mutations are sufficient to achieve higher-affinities. One mutation in a residue (Valpha1) outside of the CDRs, also generated a higher affinity, peptide specific TCR. Results with this and other mutants led to various predictions about the plasticity of TCRs in recognizing specific antigenic pepMHC complexes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Chlewicki, Lukasz Krzysztof

Contributors dc:contributor

• Kranz, David M.

• Health Sciences, Immunology

Language dc:language

eng

Identifier

(MiAaPQ)AAI3153268

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86669