Peptide Binding and Immunological Properties of the Molecular Chaperonin TRiC

Date of Completion

January 2010


Health Sciences, Immunology




Many heat shock proteins (HSPs) bind antigenic peptides inside cells, and these HSP-peptide complexes are essential for endogenous antigen processing for presentation on major histocompatibility complex class I (MHC I). They have also been suggested to mediate the transfer of antigen to antigen presenting cells (APCs) for cross priming of cytotoxic T lymphocytes (CTLs) against the chaperoned peptides. The TCP-1 Ring Complex (TRiC) is a eukaryotic homologue of hsp60 that has been shown to bind and protect extended antigenic peptides during processing for presentation on MHC I. However, the role of TRiC in cross priming has been heretofore uninvestigated. My hypothesis is that TRiC behaves like the other peptide binding chaperones in both its peptide binding properties and its interactions with APCs as a facilitator of cross priming. The data in this thesis demonstrate that TRiC binds to antigenic peptides in vitro and characterize the biochemical parameters of that binding. These data also demonstrate that in vitro reconstituted TRiC-peptide complexes facilitate the cross priming of CTLs specific for the TRiC chaperoned peptides. TRiC binds to APCs in vitro, and chaperoned peptides are processed and presented on MHC I. These observations provide a plausible mechanism for cross priming of peptides chaperoned by TRiC. However, while TRiC can effectively chaperone peptides into APCs for cross priming, the data here suggest that TRiC does not bind sufficient quantities of antigenic peptide inside the cell to facilitate cross presentation or cross priming of these endogenously bound peptides. ^