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Science 28 May 2004:
Vol. 304. no. 5675, pp. 1318 - 1321
DOI: 10.1126/science.1096378
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Reports

CD8+ T Cell Cross-Priming via Transfer of Proteasome Substrates

Christopher C. Norbury,1,2,3* Sameh Basta,1*{dagger} Keri B. Donohue,2,3 David C. Tscharke,1{ddagger} Michael F. Princiotta,1 Peter Berglund,1 James Gibbs,1 Jack R. Bennink,1 Jonathan W. Yewdell1§

"Cross-priming" describes the activation of naïve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell–derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.

1 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, 20892–0440, USA.
2 Department of Microbiology and Immunology, Pennsylvania State University Huck Institute for Life Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
3 Integrative Biosciences Graduate Program, Option in Molecular Medicine, Pennsylvania State University Huck Institute for Life Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.



* These authors contributed equally to this work.

{dagger} Present address: Division of Immunology, Biology Department, University of Constance, D-78457 Constance, Germany.

{ddagger} Present address: Epstein-Barr Virus Biology Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.

§ To whom correspondence should be addressed. E-mail: jyewdell{at}niaid.nih.gov

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