{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/86669"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/86669","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Structure, Function and Engineering of Peptide -Mhc Binding Receptors","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Chlewicki, Lukasz Krzysztof"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Microbiology","degree_department":null,"school":null,"contributors":["Kranz, David M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-28T15:17:18Z","date_published":"2015-09-28T15:17:18Z","updated_at":"2026-07-22T22:26:27Z","subjects":["Health Sciences, Immunology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3153268"],"render_values":[{"text":"(MiAaPQ)AAI3153268","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/86669","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kranz, David M."]},{"key":"dc:creator","label":"Author","values":["Chlewicki, Lukasz Krzysztof"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-28T15:17:18Z","10000-01-01","2004"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences, Immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/86669","(MiAaPQ)AAI3153268"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","Made available in DSpace on 2015-09-28T15:17:18Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3153268.pdf: 9007251 bytes, checksum: 71009314e07173981629621cff26c494 (MD5) Previous issue date: 2004","Embargo set by: Seth Robbins for item 87950 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","206 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2004."]},{"key":"dc:title","label":"Title","values":["Structure, Function and Engineering of Peptide -Mhc Binding Receptors"]}]}],"canonical_facts":{"dc:contributor":["Kranz, David M."],"dc:creator":["Chlewicki, Lukasz Krzysztof"],"dc:date":["2015-09-28T15:17:18Z","10000-01-01","2004"],"dc:description":["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. 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