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Murine epithelial glycoprotein differentially modulates MHC class II-restricted antigen presentation by dendritic cells and macrophages / Shaheen Sutterwala.
Holman Biotech Commons Thesis S967 2003
Available
LIBRA Diss. POPM2003.234
Available from offsite location
- Format:
- Book
- Manuscript
- Microformat
- Thesis/Dissertation
- Author/Creator:
- Sutterwala, Shaheen.
- Language:
- English
- Subjects (All):
- Penn dissertations--Immunology.
- Immunology--Penn dissertations.
- Allergy and Immunology.
- Academic Dissertations as Topic.
- Medical Subjects:
- Allergy and Immunology.
- Academic Dissertations as Topic.
- Local Subjects:
- Penn dissertations--Immunology.
- Immunology--Penn dissertations.
- Physical Description:
- xi, 150 pages : illustrations ; 29 cm
- Production:
- 2003.
- Summary:
- The tumor-associated antigen GA733-2 is expressed at high levels by many epithelial tumors and at low levels by normal epithelial tissue and some antigen presenting cells (APCs), including subsets of dendritic cells (DCs). The ectopic expression of GA733-2 and its murine orthologue mEGP by human monocyte derived DCs and murine bone marrow derived DCs, respectively, has previously been shown to inhibit their ability to stimulate CD4+ T cells. Using a different APC type, the macrophage (M&phis;), we now find that in contrast to DCs, the ectopic expression of mEGP by the RAW 264.7 M&phis; cell line and primary bone marrow derived M&phis;s correlates with an enhancement of their capacity to activate CD4+ T cells. Analysis of both mEGPexpressing DCs and M&phis;s revealed no significant alterations in surface levels of peptide loaded MHC class II complexes, costimulation or adhesion molecules, that might serve to explain their altered antigen presentation capabilities. However, cell staining revealed actin cytoskeletal rearrangements in both mEGP-expressing DCs and M&phis;s. The effects of actin cytoskeletal rearrangements on APC cell shape and polarity are highly cell type specific and more importantly, may impact on the cognate interaction between APCs and T cells that is a prerequisite for T cell activation. Our results support a model where cell type specific alterations of the APC actin cytoskeleton mediated by mEGP may be responsible for the differential modulation of antigen presentation in mEGP-expressing DCs and M&phis;s.
- Notes:
- Supervisor: Michael S. Marks.
- Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2003.
- Includes bibliographical references.
- Local Notes:
- University Microfilms order no.: 3095951.
- OCLC:
- 244973040
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