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Science 319 (5860): 215-220

Copyright © 2008 by the American Association for the Advancement of Science

Recognition of a Ubiquitous Self Antigen by Prostate Cancer-Infiltrating CD8+ T Lymphocytes

Peter A. Savage,1 Keith Vosseller,2 Chulho Kang,3 Kevin Larimore,4 Elyn Riedel,5 Kathleen Wojnoonski,1 Achim A. Jungbluth,6 James P. Allison1*

Abstract: Substantial evidence exists that many tumors can be specifically recognized by CD8+ T lymphocytes. The definition of antigens targeted by these cells is paramount for the development of effective immunotherapeutic strategies for treating human cancers. In a screen for endogenous tumor-associated T cell responses in a primary mouse model of prostatic adenocarcinoma, we identified a naturally arising CD8+ T cell response that is reactive to a peptide derived from histone H4. Despite the ubiquitous nature of histones, T cell recognition of histone H4 peptide was specifically associated with the presence of prostate cancer in these mice. Thus, the repertoire of antigens recognized by tumor-infiltrating T cells is broader than previously thought and includes peptides derived from ubiquitous self antigens that are normally sequestered from immune detection.

1 Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY 10021, USA.
2 Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
3 Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
4 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
5 Department of Epidemiology and Biostatistics, MSKCC, New York, NY 10065, USA.
6 New York Branch, Ludwig Institute for Cancer Research, New York, NY 10021, USA.

* To whom correspondence should be addressed. E-mail: allisonj{at}mskcc.org


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