Show simple item record

dc.contributor.advisor Blum, Janice S en_US Houlihan, Josetta Lynn en_US 2010-06-15T16:57:44Z 2027-02-15T17:57:44Z 2012-03-07T02:09:06Z 2010-06-15T16:57:44Z 2009 en_US
dc.description Thesis (Ph.D.) - Indiana University, Microbiology & Immunology, 2009 en_US
dc.description.abstract The function of major histocompatability complex (MHC) class II molecules is to present antigenic peptides to CD4+ T cells. Typically, MHC class II molecules present peptides derived from exogenous sources. Yet, certain endogenous antigens (Ags) have been found to be presented by class II molecules. Studies suggest that specific heat shock protein family members may play a role in Ag processing and subsequent class II presentation. The studies presented here using B lymphoblasts demonstrate the importance of HSP90α, HSP90β, and possibly HSP70 in selectively regulating MHC class II presentation. Inactivation of HSP90 function using pharmacological inhibitors inhibited class II presentation of exogenous and endogenous GAD, but did not perturb the presentation of several other intra- and extracellular Ags. Individual knockdown of HSP90 isoforms using isoform specific siRNA selectively inhibited GAD Ag presentation. These results demonstrate a requirement for HSP90α and HSP90β in regulating MHC class II presentation of select Ags. Studies to explore mechanistically the roles of HSP90α and HSP90β in regulating GAD Ag presentation were pursued. The pathways of exogenous and endogenous MHC class II presentation of GAD Ag are distinct yet converge with shared terminal processing of GAD within endosomal/lysosomal vesicles. The effect of HSP90 manipulation on various shared components of the MHC class II pathway was examined. The studies presented here suggest that HSP90α and HSP90β regulate MHC class II presentation of GAD Ag at discrete steps most likely involving HSP90 binding to GAD Ag rather than perturbing overall MHC class II function. Studying the role of HSP90 in MHC class II presentation in B cells revealed the potential requirement for HSP70 in the presentation of select Ags. The studies presented here demonstrate a possible role for HSP70 in the presentation of Ags such as SMA or Ig kappa by MHC class II molecules. Also included in this work is a study of a rare case of diabetes caused by type B insulin resistance due to development of insulin receptor autoantibodies during the treatment of hepatitis C with interferon alpha and ribavirin. Clinical and laboratory findings in the case are presented. en_US
dc.language.iso EN en_US
dc.publisher [Bloomington, Ind.] : Indiana University en_US
dc.subject Heat Shock Proteins en_US
dc.subject B cells en_US
dc.subject MHC Class II Presentation en_US
dc.subject Antigen Presentation en_US
dc.subject.classification Biology, Molecular en_US
dc.subject.classification Biology, Cell en_US
dc.subject.classification Biology, Microbiology en_US
dc.title The Role of HSPs in MHC Class II Presentation of Select Antigens en_US
dc.type Doctoral Dissertation en_US

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search IUScholarWorks

Advanced Search


My Account