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dc.contributor.advisorLawrence J. Stern
dc.contributor.authorNegroni, Maria P.
dc.date2022-08-11T08:08:47.000
dc.date.accessioned2022-08-23T16:08:08Z
dc.date.available2022-08-23T16:08:08Z
dc.date.issued2018-07-03
dc.date.submitted2018-09-24
dc.identifier.doi10.13028/qzt0-1d74
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32385
dc.description.abstractAntigen presentation and recognition are key processes of the immune system necessary to initiate the adaptive immune response. Longstanding goals of these fields have been to understand the molecular mechanism of MHC II-peptide binding, the way in which dysregulation of this process can lead to disease, and determining how γδTCRs recognize their ligands. To examine some of these outstanding questions, I designed photocleavable peptides that could bind HLA-DR1 and could be used to facilitate peptide exchange. I also performed studies to understand whether peptide exchange on HLA-DR1 can be affected by glycation modifications, which occur in hyperglycemic conditions such as diabetes. I observed that while glycation modifications on HLA-DR1 did not affect peptide exchange, these modifications decreased the catalytic effect of HLA-DM on this reaction, which could affect antigen presentation in diabetic patients. For studies on antigen recognition by γδTCRs, I focused on γδNKT cells, a subset of γδT cells known to play a role during Listeria infection. I used four different variants of the γδNKT TCR to study the restrictions on Vγ junctional region usage by this TCR for ligand recognition. I found that all the TCR variants I examined could recognize cells infected with Listeria, indicating that this TCR is not restricted by γ-chain usage in order to recognize ligand. My research generated reagents that could serve in future studies of HLA-DR1 peptide binding and contributed to understanding the effect of hyperglycemic conditions on antigen presentation, as well as provided greater understanding of γδTCR restriction for ligand recognition.
dc.language.isoen_US
dc.rightsLicensed under a Creative Commons license
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntigen
dc.subjectHLA-DR
dc.subjectglycation
dc.subjectphotocleavable peptide
dc.subjectpeptide
dc.subjectbinding kinetics
dc.subjectgamma delta T cells
dc.subjectTCR
dc.subjectligand
dc.subjectListeria
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectImmunology and Infectious Disease
dc.titleStudies in Antigen Presentation and Antigen Recognition at Different Interfaces of the Adaptive Immune System
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2003&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/996
dc.legacy.embargo2018-09-24T00:00:00-07:00
dc.identifier.contextkey12925518
refterms.dateFOA2022-08-26T03:32:28Z
html.description.abstract<p>Antigen presentation and recognition are key processes of the immune system necessary to initiate the adaptive immune response. Longstanding goals of these fields have been to understand the molecular mechanism of MHC II-peptide binding, the way in which dysregulation of this process can lead to disease, and determining how γδTCRs recognize their ligands. To examine some of these outstanding questions, I designed photocleavable peptides that could bind HLA-DR1 and could be used to facilitate peptide exchange. I also performed studies to understand whether peptide exchange on HLA-DR1 can be affected by glycation modifications, which occur in hyperglycemic conditions such as diabetes. I observed that while glycation modifications on HLA-DR1 did not affect peptide exchange, these modifications decreased the catalytic effect of HLA-DM on this reaction, which could affect antigen presentation in diabetic patients. For studies on antigen recognition by γδTCRs, I focused on γδNKT cells, a subset of γδT cells known to play a role during <em>Listeria </em>infection. I used four different variants of the γδNKT TCR to study the restrictions on Vγ junctional region usage by this TCR for ligand recognition. I found that all the TCR variants I examined could recognize cells infected with <em>Listeria</em>, indicating that this TCR is not restricted by γ-chain usage in order to recognize ligand. My research generated reagents that could serve in future studies of HLA-DR1 peptide binding and contributed to understanding the effect of hyperglycemic conditions on antigen presentation, as well as provided greater understanding of γδTCR restriction for ligand recognition.</p>
dc.identifier.submissionpathgsbs_diss/996
dc.contributor.departmentPathology
dc.description.thesisprogramBiochemistry and Molecular Pharmacology
dc.identifier.orcid0000-0001-8771-3246


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