Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Phire Hot Start DNA Polymerase

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 28 May 2004:
Vol. 304. no. 5675, pp. 1318 - 1321
DOI: 10.1126/science.1096378
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Derivation and Fluidity of Acutely Induced Dysfunctional CD8+ T Cells.
G. Plesa, A. E. Snook, S. A. Waldman, and L. C. Eisenlohr (2008)
J. Immunol. 180, 5300-5308
   Abstract »    Full Text »    PDF »
Targeting Tumor Antigens to Secreted Membrane Vesicles In vivo Induces Efficient Antitumor Immune Responses.
I. S. Zeelenberg, M. Ostrowski, S. Krumeich, A. Bobrie, C. Jancic, A. Boissonnas, A. Delcayre, J.-B. Le Pecq, B. Combadiere, S. Amigorena, et al. (2008)
Cancer Res. 68, 1228-1235
   Abstract »    Full Text »    PDF »
Kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes.
E. Assarsson, J. A. Greenbaum, M. Sundstrom, L. Schaffer, J. A. Hammond, V. Pasquetto, C. Oseroff, R. C. Hendrickson, E. J. Lefkowitz, D. C. Tscharke, et al. (2008)
PNAS 105, 2140-2145
   Abstract »    Full Text »    PDF »
Targeting HIV-1 Gag into the Defective Ribosomal Product Pathway Enhances MHC Class I Antigen Presentation and CD8+ T Cell Activation.
A. Goldwich, S. S. C. Hahn, S. Schreiber, S. Meier, E. Kampgen, R. Wagner, M. B. Lutz, and U. Schubert (2008)
J. Immunol. 180, 372-382
   Abstract »    Full Text »    PDF »
N-Terminal Trimer Extension of Nominal CD8 T Cell Epitopes Is Sufficient to Promote Cross-Presentation to Cognate CD8 T Cells In Vivo.
C.-H. Wei and L. A. Sherman (2007)
J. Immunol. 179, 8280-8286
   Abstract »    Full Text »    PDF »
Prolonged Antigen Expression following DNA Vaccination Impairs Effector CD8+ T Cell Function and Memory Development.
J. N. Radcliffe, J. S. Roddick, F. K. Stevenson, and S. M. Thirdborough (2007)
J. Immunol. 179, 8313-8321
   Abstract »    Full Text »    PDF »
Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells.
F. Dzierszinski, M. Pepper, J. S. Stumhofer, D. F. LaRosa, E. H. Wilson, L. A. Turka, S. K. Halonen, C. A. Hunter, and D. S. Roos (2007)
Infect. Immun. 75, 5200-5209
   Abstract »    Full Text »    PDF »
Cross-Priming of Cytotoxic T Cells Dictates Antigen Requisites for Modified Vaccinia Virus Ankara Vector Vaccines.
G. Gasteiger, W. Kastenmuller, R. Ljapoci, G. Sutter, and I. Drexler (2007)
J. Virol. 81, 11925-11936
   Abstract »    Full Text »    PDF »
Increasing the Survival of Dendritic Cells In Vivo Does Not Replace the Requirement for CD4+ T Cell Help during Primary CD8+ T Cell Responses.
K. E. Matthews, J. S. Qin, J. Yang, I. F. Hermans, M. J. Palmowski, V. Cerundolo, and F. Ronchese (2007)
J. Immunol. 179, 5738-5747
   Abstract »    Full Text »    PDF »
TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-{gamma} production.
R. S. Goldszmid, A. Bafica, D. Jankovic, C. G. Feng, P. Caspar, R. Winkler-Pickett, G. Trinchieri, and A. Sher (2007)
J. Exp. Med. 204, 2591-2602
   Abstract »    Full Text »    PDF »
Antigen Presentation by Exosomes Released from Peptide-Pulsed Dendritic Cells Is not Suppressed by the Presence of Active CTL.
L. Luketic, J. Delanghe, P. T. Sobol, P. Yang, E. Frotten, K. L. Mossman, J. Gauldie, J. Bramson, and Y. Wan (2007)
J. Immunol. 179, 5024-5032
   Abstract »    Full Text »    PDF »
Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells.
S. Koido, E. Hara, S. Homma, M. Mitsunaga, A. Takahara, E. Nagasaki, H. Kawahara, M. Watanabe, Y. Toyama, S. Yanagisawa, et al. (2007)
J. Immunol. 179, 4874-4883
   Abstract »    Full Text »    PDF »
Structure and Function: Heat Shock Proteins and Adaptive Immunity.
B. Javid, P. A. MacAry, and P. J. Lehner (2007)
J. Immunol. 179, 2035-2040
   Abstract »    Full Text »    PDF »
In Vivo Antigen Stability Affects DNA Vaccine Immunogenicity.
A. D. Bins, M. C. Wolkers, M. D. van den Boom, J. B. A. G. Haanen, and T. N. M. Schumacher (2007)
J. Immunol. 179, 2126-2133
   Abstract »    Full Text »    PDF »
Molecular and Cellular Requirements for Enhanced Antigen Cross-Presentation to CD8 Cytotoxic T Lymphocytes.
S. Oizumi, N. Strbo, S. Pahwa, V. Deyev, and E. R. Podack (2007)
J. Immunol. 179, 2310-2317
   Abstract »    Full Text »    PDF »
A lymphocytic choriomeningitis virus glycoprotein variant that is retained in the endoplasmic reticulum efficiently cross-primes CD8+ T cell responses.
S. Freigang, B. Eschli, N. Harris, M. Geuking, K. Quirin, S. Schrempf, R. Zellweger, J. Weber, H. Hengartner, and R. M. Zinkernagel (2007)
PNAS 104, 13426-13431
   Abstract »    Full Text »    PDF »
Viral Alteration of Cellular Translational Machinery Increases Defective Ribosomal Products.
P. Berglund, D. Finzi, J. R. Bennink, and J. W. Yewdell (2007)
J. Virol. 81, 7220-7229
   Abstract »    Full Text »    PDF »
A novel proteoliposomal vaccine elicits potent antitumor immunity in mice.
M. C. Popescu, R. J. Robb, M. M. Batenjany, L. T. Boni, M. E. Neville, R. W. Pennington, S. S. Neelapu, and L. W. Kwak (2007)
Blood 109, 5407-5410
   Abstract »    Full Text »    PDF »
Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection.
M. W. Munks, A. K. Pinto, C. M. Doom, and A. B. Hill (2007)
J. Immunol. 178, 7235-7241
   Abstract »    Full Text »    PDF »
Bortezomib enhances dendritic cell (DC) mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications.
R. Spisek, A. Charalambous, A. Mazumder, D. H. Vesole, S. Jagannath, and M. V. Dhodapkar (2007)
Blood 109, 4839-4845
   Abstract »    Full Text »    PDF »
Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation.
S. Burgdorf, A. Kautz, V. Bohnert, P. A. Knolle, and C. Kurts (2007)
Science 316, 612-616
   Abstract »    Full Text »    PDF »
Efficiency of peptide presentation by dendritic cells compared with other cell types: implications for cross-priming.
D. Zehn, C. J. Cohen, Y. Reiter, and P. Walden (2006)
Int. Immunol. 18, 1647-1654
   Abstract »    Full Text »    PDF »
Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells.
J. N. Radcliffe, J. S. Roddick, P. S. Friedmann, F. K. Stevenson, and S. M. Thirdborough (2006)
J. Immunol. 177, 6626-6633
   Abstract »    Full Text »    PDF »
Dendritic Cells Cross-Dressed with Peptide MHC Class I Complexes Prime CD8+ T Cells.
B. P. Dolan, K. D. Gibbs Jr, and S. Ostrand-Rosenberg (2006)
J. Immunol. 177, 6018-6024
   Abstract »    Full Text »    PDF »
Leishmania Antigens Are Presented to CD8+ T Cells by a Transporter Associated with Antigen Processing-Independent Pathway In Vitro and In Vivo.
S. Bertholet, R. Goldszmid, A. Morrot, A. Debrabant, F. Afrin, C. Collazo-Custodio, M. Houde, M. Desjardins, A. Sher, and D. Sacks (2006)
J. Immunol. 177, 3525-3533
   Abstract »    Full Text »    PDF »
Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response.
M. Prlic, G. Hernandez-Hoyos, and M. J. Bevan (2006)
J. Exp. Med. 203, 2135-2143
   Abstract »    Full Text »    PDF »
Role of Immunoproteasomes in Cross-Presentation.
M. J. Palmowski, U. Gileadi, M. Salio, A. Gallimore, M. Millrain, E. James, C. Addey, D. Scott, J. Dyson, E. Simpson, et al. (2006)
J. Immunol. 177, 983-990
   Abstract »    Full Text »    PDF »
Immunogenicity of cytopathic and noncytopathic viral vectors..
G. Plesa, P. M. McKenna, M. J. Schnell, and L. C. Eisenlohr (2006)
J. Virol. 80, 6259-6266
   Abstract »    Full Text »    PDF »
CD1d-Restricted T Cells License B Cells to Generate Long-Lasting Cytotoxic Antitumor Immunity In vivo..
Y. Chung, B.-S. Kim, Y.-J. Kim, H.-J. Ko, S.-Y. Ko, D.-H. Kim, and C.-Y. Kang (2006)
Cancer Res. 66, 6843-6850
   Abstract »    Full Text »    PDF »
The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional antigen-presenting cells.
C. Biswas, U. Sriram, B. Ciric, O. Ostrovsky, S. Gallucci, and Y. Argon (2006)
Int. Immunol. 18, 1147-1157
   Abstract »    Full Text »    PDF »
Processing of Tumor-Associated Antigen by the Proteasomes of Dendritic Cells Controls In vivo T-Cell Responses..
L. Chapatte, M. Ayyoub, S. Morel, A.-L. Peitrequin, N. Levy, C. Servis, B. J. Van den Eynde, D. Valmori, and F. Levy (2006)
Cancer Res. 66, 5461-5468
   Abstract »    Full Text »    PDF »
Immunogenic Cell Death and Cross-Priming Are Reaching the Clinical Immunotherapy Arena.
I. Melero, A. Arina, O. Murillo, J. Dubrot, C. Alfaro, J. L. Perez-Gracia, M. Bendandi, and S. Hervas-Stubbs (2006)
Clin. Cancer Res. 12, 2385-2389
   Full Text »    PDF »
Hyperthermia Enhances CTL Cross-Priming.
H. Shi, T. Cao, J. E. Connolly, L. Monnet, L. Bennett, S. Chapel, C. Bagnis, P. Mannoni, J. Davoust, A. K. Palucka, et al. (2006)
J. Immunol. 176, 2134-2141
   Abstract »    Full Text »    PDF »
Cranking the Immunologic Engine with Chemotherapy: Using Context to Drive Tumor Antigen Cross-Presentation towards Useful Antitumor Immunity.
R. G. van der Most, A. Currie, B. W.S. Robinson, and R. A. Lake (2006)
Cancer Res. 66, 601-604
   Abstract »    Full Text »    PDF »
The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to the trans-Golgi Network and Promotes an Efficient Presentation through HLA Class I.
F. Bettosini, M. T. Fiorillo, A. Magnacca, L. Leone, M. R. Torrisi, and R. Sorrentino (2005)
J. Virol. 79, 15537-15546
   Abstract »    Full Text »    PDF »
Antitumor Activity of Human Papillomavirus Type 16 E7-Specific T Cells against Virally Infected Squamous Cell Carcinoma of the Head and Neck.
A. Albers, K. Abe, J. Hunt, J. Wang, A. Lopez-Albaitero, C. Schaefer, W. Gooding, T. L. Whiteside, S. Ferrone, A. DeLeo, et al. (2005)
Cancer Res. 65, 11146-11155
   Abstract »    Full Text »    PDF »
Identification of the Immunodominant HY H2-Dk Epitope and Evaluation of the Role of Direct and Indirect Antigen Presentation in HY Responses.
M. Millrain, D. Scott, C. Addey, H. Dewchand, P. Ellis, I. Ehrmann, M. Mitchell, P. Burgoyne, E. Simpson, and J. Dyson (2005)
J. Immunol. 175, 7209-7217
   Abstract »    Full Text »    PDF »
Tissue-Resident Memory CD8+ T Cells Can Be Deleted by Soluble, but Not Cross-Presented Antigen.
C.-H. Wei, R. Trenney, M. Sanchez-Alavez, K. Marquardt, D. L. Woodland, S. J. Henriksen, and L. A. Sherman (2005)
J. Immunol. 175, 6615-6623
   Abstract »    Full Text »    PDF »
Protein Transduction of Dendritic Cells for NY-ESO-1-Based Immunotherapy of Myeloma.
R. B. Batchu, A. M. Moreno, S. M. Szmania, G. Bennett, G. C. Spagnoli, S. Ponnazhagan, B. Barlogie, G. Tricot, and F. van Rhee (2005)
Cancer Res. 65, 10041-10049
   Abstract »    Full Text »    PDF »
Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo.
D. Accapezzato, V. Visco, V. Francavilla, C. Molette, T. Donato, M. Paroli, M. U. Mondelli, M. Doria, M. R. Torrisi, and V. Barnaba (2005)
J. Exp. Med. 202, 817-828
   Abstract »    Full Text »    PDF »
Turning On/Off Tumor-Specific CTL Response during Progressive Tumor Growth.
Y. Huang, N. Obholzer, R. Fayad, and L. Qiao (2005)
J. Immunol. 175, 3110-3116
   Abstract »    Full Text »    PDF »
Inefficient Cross-Presentation Limits the CD8+ T Cell Response to a Subdominant Tumor Antigen Epitope.
P. Otahal, S. C. Hutchinson, L. M. Mylin, M. J. Tevethia, S. S. Tevethia, and T. D. Schell (2005)
J. Immunol. 175, 700-712
   Abstract »    Full Text »    PDF »
Cross-Presentation of the Long-Lived Lymphocytic Choriomeningitis Virus Nucleoprotein Does Not Require Neosynthesis and Is Enhanced via Heat Shock Proteins.
S. Basta, R. Stoessel, M. Basler, M. van den Broek, and M. Groettrup (2005)
J. Immunol. 175, 796-805
   Abstract »    Full Text »    PDF »
Mouse Endothelial Cells Cross-Present Lymphocyte-Derived Antigen on Class I MHC via a TAP1- and Proteasome-Dependent Pathway.
R. Bagai, A. Valujskikh, D. H. Canaday, E. Bailey, P. N. Lalli, C. V. Harding, and P. S. Heeger (2005)
J. Immunol. 174, 7711-7715
   Abstract »    Full Text »    PDF »
Delayed Disease Progression after Allogeneic Cell Vaccination in Hormone-Resistant Prostate Cancer and Correlation with Immunologic Variables.
A. Michael, G. Ball, N. Quatan, F. Wushishi, N. Russell, J. Whelan, P. Chakraborty, D. Leader, M. Whelan, and H. Pandha (2005)
Clin. Cancer Res. 11, 4469-4478
   Abstract »    Full Text »    PDF »
Pseudovirion Particle Production by Live Poxvirus Human Immunodeficiency Virus Vaccine Vector Enhances Humoral and Cellular Immune Responses.
X. Chen, M. T. Rock, J. Hammonds, J. Tartaglia, A. Shintani, J. Currier, B. Slike, J. E. Crowe Jr., M. Marovich, and P. Spearman (2005)
J. Virol. 79, 5537-5547
   Abstract »    Full Text »    PDF »
Regulatory T Cells Suppress CD8+ T Cell Responses Induced by Direct Priming and Cross-Priming and Moderate Immunodominance Disparities.
S. M. M. Haeryfar, R. J. DiPaolo, D. C. Tscharke, J. R. Bennink, and J. W. Yewdell (2005)
J. Immunol. 174, 3344-3351
   Abstract »    Full Text »    PDF »
Immunization with Lentiviral Vector-Transduced Dendritic Cells Induces Strong and Long-Lasting T Cell Responses and Therapeutic Immunity.
Y. He, J. Zhang, Z. Mi, P. Robbins, and L. D. Falo Jr (2005)
J. Immunol. 174, 3808-3817
   Abstract »    Full Text »    PDF »
The Impact of Misfolding versus Targeted Degradation on the Efficiency of the MHC Class I-Restricted Antigen Processing.
T. N. Golovina, S. E. Morrison, and L. C. Eisenlohr (2005)
J. Immunol. 174, 2763-2769
   Abstract »    Full Text »    PDF »
Class I Major Histocompatibility Complex Presentation of Antigens That Escape from the Parasitophorous Vacuole of Toxoplasma gondii.
M.-J. Gubbels, B. Striepen, N. Shastri, M. Turkoz, and E. A. Robey (2005)
Infect. Immun. 73, 703-711
   Abstract »    Full Text »    PDF »
SREC-I, a Type F Scavenger Receptor, Is an Endocytic Receptor for Calreticulin.
B. Berwin, Y. Delneste, R. V. Lovingood, S. R. Post, and S. V. Pizzo (2004)
J. Biol. Chem. 279, 51250-51257
   Abstract »    Full Text »    PDF »
Cutting Edge: Cross-Presentation of Cell-Associated Antigens to MHC Class I Molecule Is Regulated by a Major Transcription Factor for Heat Shock Proteins.
H. Zheng and Z. Li (2004)
J. Immunol. 173, 5929-5933
   Abstract »    Full Text »    PDF »
Cross-Presentation of Listeria-Derived CD8 T Cell Epitopes Requires Unstable Bacterial Translation Products.
J. Janda, P. Schoneberger, M. Skoberne, M. Messerle, H. Russmann, and G. Geginat (2004)
J. Immunol. 173, 5644-5651
   Abstract »    Full Text »    PDF »
IL-4 deficiency does not impair the ability of dendritic cells to initiate CD4+ and CD8+ T cell responses in vivo.
J. M. Roberts, J. Yang, and F. Ronchese (2004)
Int. Immunol. 16, 1451-1458
   Abstract »    Full Text »    PDF »
Antigen Bias in T Cell Cross-Priming.
M. C. Wolkers, N. Brouwenstijn, A. H. Bakker, M. Toebes, and T. N. M. Schumacher (2004)
Science 304, 1314-1317
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)