Human papillomavirus type 16 E7 oncoprotein expressed in peripheral epithelium tolerizes E7-directed cytotoxic T-lymphocyte precursors restricted through human (and mouse) major histocompatibility complex class I alleles

Doan, Tracy, Herd, Karen, Street, Michael, Bryson, Gregory, Fernando, Germain, Lambert, Paul and Tindle, Robert (1999) Human papillomavirus type 16 E7 oncoprotein expressed in peripheral epithelium tolerizes E7-directed cytotoxic T-lymphocyte precursors restricted through human (and mouse) major histocompatibility complex class I alleles. Journal of Virology, 73 7: 6166-6170.

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Author Doan, Tracy
Herd, Karen
Street, Michael
Bryson, Gregory
Fernando, Germain
Lambert, Paul
Tindle, Robert
Title Human papillomavirus type 16 E7 oncoprotein expressed in peripheral epithelium tolerizes E7-directed cytotoxic T-lymphocyte precursors restricted through human (and mouse) major histocompatibility complex class I alleles
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 1999-07
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 73
Issue 7
Start page 6166
End page 6170
Total pages 5
Editor Thomas E. Shenk
Place of publication Washington, USA
Publisher American Society for Microbiology
Collection year 1999
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
Abstract Mice which coexpress human papillomavirus type 16 E7 and HLA A2.1 in peripheral squamous epithelium and thymic cortical epithelium are tolerant at the cytotoxic T-lymphocyte (CTL) level to E7 epitopes restricted through HLA A*0201 and H-2(b) (T. Doan, M. Chambers, M. Street, G. J. Fernando, If. Herd, P. Lambert, and R. Tindle, Virology 244:352-364, 1998), Here we used bone marrow-reconstituted radiation chimeras to distinguish whether E7-directed CTL tolerance was mediated peripherally by E7 expression in skin or centrally by E7 expression in thymus. In chimeric mice expressing E7 in skin and reconstituted with E7-naive bone marrow and E7-naive thymus, CTL responses to vaccine-administered E7 epitopes mere not restored, i.e., the mice remained tolerant. In contrast, chimeric mice not expressing E7 in skin and reconstituted with E7-naive bone marrow and E7-expressing thymus had fail E7-directed CTL responses. These results demonstrate that E7 protein expression in peripheral squamous epithelium is sufficient to tolerize the E7-directed CTL precursor repertoire. The data have implications for E7-mediated tumorigenesis and for the development of E7-based immunotherapeutic strategies, since peripheral immunological tolerance of tumor-associated antigens may create a barrier to effective immunotherapy.
Keyword Virology
Transgenic Mice
Cell Tolerance
Cervical-cancer
Cross-presentation
Self-antigens
Induction
Epitope
Keratinocytes
Autoimmunity
Responses
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Tue, 10 Jun 2008, 13:46:11 EST