Graduate School of Biomedical Sciences, Program in Immunology and Virology
Dissertations, UMMS; Histocompatibility Antigens Class I; Antigen Presentation; CD8-Positive T-Lymphocytes; Ribosomes
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
Farfán Arribas, Diego José, "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.