Show simple item record

dc.contributor.advisorKenneth L. Rock, M.D.
dc.contributor.authorFarfán Arribas, Diego José
dc.date2022-08-11T08:08:43.000
dc.date.accessioned2022-08-23T16:05:45Z
dc.date.available2022-08-23T16:05:45Z
dc.date.issued2012-04-04
dc.date.submitted2012-05-14
dc.identifier.doi10.13028/23eg-3c30
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31933
dc.description.abstractPeptides generated from cellular protein degradation via the ubiquitin-proteasome pathway are presented on MHC class I as a means for the immune system to monitor polypeptides being synthesized by cells. For CD8 + T cells to prevent the spread of an incipient infection, it appears essential they should be able to sense foreign polypeptides being synthesized as soon as possible. A prompt detection of viral proteins is of great importance for the success of an adaptive immune response. Defective ribosomal products (DRiPs) have been postulated as a preferential source which would allow for a rapid presentation of peptides derived from the degradation of all newly synthesized proteins. Although this hypothesis is intellectually appealing there is lack of experimental data supporting a mechanism that would prioritize presentation from DRiPs. In this dissertation I describe a series of experiments that probe the DRiPs hypothesis by assessing the contribution to class I presentation of model epitopes derived from DRiPs or from functional proteins. The results show that even at the early stages after mRNA synthesis DRiPs do not account for a significant fraction of the class I presented peptides. These observations suggest that the currently widespread model whereby a mechanism exists which selectively allows for DRiPs to preferentially contribute to class I antigen presentation, is incorrect. Rather, properly folded functional proteins can significantly contribute to class I antigen presentation as they are normally turned over by the ubiquitin-proteasome pathway.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectHistocompatibility Antigens Class I
dc.subjectAntigen Presentation
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectRibosomes
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiological Factors
dc.subjectCells
dc.subjectHemic and Immune Systems
dc.subjectImmunology and Infectious Disease
dc.titleOn the Source of Peptides for Major Histocompatibility Class I Antigen Presentation: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1591&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/589
dc.legacy.embargo2013-05-07T00:00:00-07:00
dc.identifier.contextkey2847889
refterms.dateFOA2022-08-28T03:42:16Z
html.description.abstract<p>Peptides generated from cellular protein degradation via the ubiquitin-proteasome pathway are presented on MHC class I as a means for the immune system to monitor polypeptides being synthesized by cells. For CD8 <sup>+</sup> T cells to prevent the spread of an incipient infection, it appears essential they should be able to sense foreign polypeptides being synthesized as soon as possible. A prompt detection of viral proteins is of great importance for the success of an adaptive immune response. Defective ribosomal products (DRiPs) have been postulated as a preferential source which would allow for a rapid presentation of peptides derived from the degradation of all newly synthesized proteins. Although this hypothesis is intellectually appealing there is lack of experimental data supporting a mechanism that would prioritize presentation from DRiPs. In this dissertation I describe a series of experiments that probe the DRiPs hypothesis by assessing the contribution to class I presentation of model epitopes derived from DRiPs or from functional proteins. The results show that even at the early stages after mRNA synthesis DRiPs do not account for a significant fraction of the class I presented peptides. These observations suggest that the currently widespread model whereby a mechanism exists which selectively allows for DRiPs to preferentially contribute to class I antigen presentation, is incorrect. Rather, properly folded functional proteins can significantly contribute to class I antigen presentation as they are normally turned over by the ubiquitin-proteasome pathway.</p>
dc.identifier.submissionpathgsbs_diss/589
dc.contributor.departmentPathology
dc.description.thesisprogramImmunology and Microbiology


Files in this item

Thumbnail
Name:
FarfanArribas_Diego_reduced.pdf
Size:
3.338Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record