GSBS Dissertations and Theses
Title
On the Source of Peptides for Major Histocompatibility Class I Antigen Presentation: A Dissertation
Publication Date
2012-04-04
Document Type
Doctoral Dissertation
Academic Program
Immunology and Microbiology
Department
Pathology
First Thesis Advisor
Kenneth L. Rock, M.D.
Keywords
Histocompatibility Antigens Class I, Antigen Presentation, CD8-Positive T-Lymphocytes, Ribosomes
Abstract
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 + 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.
Repository Citation
Farfán Arribas, DJ. On the Source of Peptides for Major Histocompatibility Class I Antigen Presentation: A Dissertation. (2012). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 589. DOI: 10.13028/23eg-3c30. https://escholarship.umassmed.edu/gsbs_diss/589
DOI
10.13028/23eg-3c30
DOI Link
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Copyright is held by the author, with all rights reserved.
Included in
Amino Acids, Peptides, and Proteins Commons, Biological Factors Commons, Cells Commons, Hemic and Immune Systems Commons, Immunology and Infectious Disease Commons