Whittle, Nicole J. (2006) Expression and recognition of HLA-DR/Her-2 complexes on carcinoma cells. Masters thesis, Memorial University of Newfoundland.
- Accepted Version
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Cancer patients frequently generate cellular immune response to Her-2, a protein implicated in promoting tumor growth. While 40% of cancers express HLA class II, the ability of class II⁺ tumor cells to process endogenous Her-2 and present immunogenic peptides for CD4⁺ T cell recognition is unknown. We addressed this question using a CD4⁺ T cell clone (TCL-6Dn) restricted to Her-2 peptide 883-899 (p883) presented by HLA-DRβ*0401. We measured the proliferation and cytokine response of TCL-6Dn to p883-loaded and Her-2⁺ tumor cells. Our results showed that TCL-6Dn proliferated strongly to p883-loaded DCs, yet TCL-6Dn lysed tumor cells in a p883-specific manner. Cytokine production analysis showed that TCL-6Dn recognized p883 and produced IFN-γ, GM-CSF, TNF-α and IL-4. Tumor cell lysis was mediated by a soluble factor produced by TCL-6Dn, but cell contact increased lysis. Furthermore, we provide evidence that p883 is a naturally processed HLA class II epitope presented by cancer cells.
|Item Type:||Thesis (Masters)|
|Additional Information:||Includes bibliographical references (leaves 108-131).|
|Department(s):||Medicine, Faculty of|
|Library of Congress Subject Heading:||Immune complexes; Tumor antigens; Tumors--Immunological aspects.|
|Medical Subject Heading:||Antigen-Antibody Complex; Antigens, Neoplasm; Neoplasms--immunology.|
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