{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:29:01Z","timestamp":1778858941047,"version":"3.51.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2001,5]]},"DOI":"10.1038\/87730","type":"journal-article","created":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T21:13:11Z","timestamp":1517346791000},"page":"423-429","source":"Crossref","is-referenced-by-count":606,"title":["Na\u00efve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation"],"prefix":"10.1038","volume":"2","author":[{"given":"Marianne J. B.","family":"van Stipdonk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E.","family":"Lemmens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Schoenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2001,5,1]]},"reference":[{"key":"BFni0501423_CR1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev.immunol.18.1.275","volume":"18","author":"JT Harty","year":"2000","unstructured":"Harty, J. T., Tvinnereim, A. R. & White, D. W. CD8+ T cell effector mechanisms in resistance to infection. Annu. Rev. Immunol. 18, 275\u2013308 (2000).","journal-title":"Annu. Rev. Immunol."},{"key":"BFni0501423_CR2","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1084\/jem.182.3.639","volume":"182","author":"MJ Bevan","year":"1995","unstructured":"Bevan, M. J. Antigen presentation to cytotoxic T lymphocytes in vivo. J. Exp. Med. 182, 639\u2013641 (1995).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR3","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/S0923-2494(99)80027-3","volume":"149","author":"A Lanzavecchia","year":"1998","unstructured":"Lanzavecchia, A. From antigen presentation to T-cell activation. Res. Immunol. 149, 626 (1998).","journal-title":"Res. Immunol."},{"key":"BFni0501423_CR4","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1146\/annurev.immunol.18.1.767","volume":"18","author":"J Banchereau","year":"2000","unstructured":"Banchereau, J. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol 18, 767\u2013811 (2000).","journal-title":"Annu. Rev. Immunol"},{"key":"BFni0501423_CR5","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1084\/jem.187.10.1549","volume":"187","author":"WR Heath","year":"1998","unstructured":"Heath, W. R., Kurts, C., Miller, J. & Carbone, F. R. Cross-tolerance: A pathway for inducing tolerance to peripheral tissue antigens. J. Exp. Med. 187, 1549\u20131553 (1998).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR6","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1084\/jem.191.11.2021","volume":"191","author":"K Garza","year":"2000","unstructured":"Garza, K. M. et al. Role of Antigen-presenting Cells in Mediating Tolerance and Autoimmunity. J. Exp. Med. 191, 2021\u20132028 (2000).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR7","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/10503","volume":"5","author":"EM Sotomayor","year":"1999","unstructured":"Sotomayor, E. M. et al. Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40. Nature Med. 5, 780\u2013787 (1999).","journal-title":"Nature Med."},{"key":"BFni0501423_CR8","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1084\/jem.155.3.768","volume":"155","author":"J Keene","year":"1982","unstructured":"Keene, J. & Forman, J. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes. J. Exp. Med. 155, 768\u2013782 (1982).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1084\/jem.186.1.65","volume":"186","author":"SRM Bennett","year":"1997","unstructured":"Bennett, S. R. M., Carbone, F. R., Karamalis, F., Miller, J. F. A. P. & Heath, W. R. Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help. J. Exp. Med. 186, 65\u201370 (1997).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR10","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/31002","volume":"393","author":"SP Schoenberger","year":"1998","unstructured":"Schoenberger, S. P. et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393, 480\u2013483 (1998).","journal-title":"Nature"},{"key":"BFni0501423_CR11","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/30996","volume":"393","author":"SR Bennett","year":"1998","unstructured":"Bennett, S. R. et al. Help for cytotoxic-T-cell responses is mediated by CD40 signaling. Nature 393 478\u2013480 (1998).","journal-title":"Nature"},{"key":"BFni0501423_CR12","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/30989","volume":"393","author":"JP Ridge","year":"1998","unstructured":"Ridge, J. P., Di Rosa, F. & Matzinger, P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393, 474\u2013478 (1998).","journal-title":"Nature"},{"key":"BFni0501423_CR13","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/15200","volume":"5","author":"S Gallucci","year":"1999","unstructured":"Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nature Med. 5, 1249\u20131255 (1999).","journal-title":"Nature Med."},{"key":"BFni0501423_CR14","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1084\/jem.189.5.821","volume":"189","author":"M Cella","year":"1999","unstructured":"Cella, M. et al. Maturation, activation and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med. 189, 821\u2013829 (1999).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR15","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1084\/jem.191.3.423","volume":"191","author":"B Sauter","year":"2000","unstructured":"Sauter, B. et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191, 423\u2013434 (2000).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR16","doi-asserted-by":"publisher","first-page":"6029","DOI":"10.4049\/jimmunol.165.11.6029","volume":"165","author":"RJ Binder","year":"2000","unstructured":"Binder, R. J., Anderson, K. M., Basu, S. & Srivastava, P. K. Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. J. Immunol. 165, 6029\u20136035 (2000).","journal-title":"J. Immunol."},{"key":"BFni0501423_CR17","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1093\/intimm\/12.11.1539","volume":"12","author":"S Basu","year":"2000","unstructured":"Basu, S., Binder, R. J., Suto, R., Anderson, K. M. & Srivastava, P. K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-\u03baB pathway. Int. Immunol. 12, 1539\u20131546 (2000).","journal-title":"Int. Immunol."},{"key":"BFni0501423_CR18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/icb.1975.3","volume":"53","author":"KJ Lafferty","year":"1975","unstructured":"Lafferty, K. J. & Cunningham, A. J. A new analysis of allogeneic interactions. Aust. J. Exp. Biol. Med. Sci. 53, 27\u201342 (1975).","journal-title":"Aust. J. Exp. Biol. Med. Sci."},{"key":"BFni0501423_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF02786473","volume":"19","author":"JM Slavik","year":"1999","unstructured":"Slavik, J. M., Hutchcroft, J. E. & Bierer, B. E. CD28\/CTLA-4 and CD80\/CD86 families: signaling and function. Immunol. Res. 19, 1\u201324 (1999).","journal-title":"Immunol. Res."},{"key":"BFni0501423_CR20","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/S0952-7915(99)00056-4","volume":"12","author":"A Lanzavecchia","year":"2000","unstructured":"Lanzavecchia, A. & Sallusto, F. From synapses to immunological memory: the role of sustained T cell stimulation. Curr. Opin. Immunol. 12, 92\u201398 (2000).","journal-title":"Curr. Opin. Immunol."},{"key":"BFni0501423_CR21","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1126\/science.283.5402.680","volume":"283","author":"A Viola","year":"1999","unstructured":"Viola, A., Schroeder, S., Sakakibara, Y. & Lanzavecchia, A. T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 283, 680\u2013682 (1999).","journal-title":"Science"},{"key":"BFni0501423_CR22","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/S1074-7613(00)80333-7","volume":"6","author":"F Borriello","year":"1997","unstructured":"Borriello, F. et al. B7\u20131 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 6, 303\u2013313 (1997).","journal-title":"Immunity"},{"key":"BFni0501423_CR23","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1128\/JVI.74.1.203-208.2000","volume":"74","author":"AJ McAdam","year":"2000","unstructured":"McAdam, A. J., Farkash, E. A., Gewurz, B. E. & Sharpe, A. H. B7 costimulation is critical for antibody class switching and CD8+ cytotoxic T-lymphocyte generation in the host response to vesicular stomatitis virus. J. Virol. 74, 203\u2013208 (2000).","journal-title":"J. Virol."},{"key":"BFni0501423_CR24","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.4049\/jimmunol.165.6.3088","volume":"165","author":"AJ McAdam","year":"2000","unstructured":"McAdam, A. J., Gewurz, B. E., Farkash, E. A. & Sharpe, A. H. Either B7 costimulation or IL-2 can elicit generation of primary alloreactive CTL. J. Immunol. 165, 3088\u20133093 (2000).","journal-title":"J. Immunol."},{"key":"BFni0501423_CR25","doi-asserted-by":"publisher","first-page":"6791","DOI":"10.4049\/jimmunol.165.12.6791","volume":"165","author":"S Santra","year":"2000","unstructured":"Santra, S. et al. Functional Equivalency of B7\u20131 and B7-2 for Costimulating Plasmid DNA Vaccine-Elicited CTL Responses. J. Immunol. 165, 6791\u20136795 (2000).","journal-title":"J. Immunol."},{"key":"BFni0501423_CR26","first-page":"23","volume":"84","author":"A Lanzavecchia","year":"1999","unstructured":"Lanzavecchia, A. Dendritic cell maturation and generation of immune responses. Haematologica 84, 23\u201325 (1999).","journal-title":"Haematologica"},{"key":"BFni0501423_CR27","first-page":"3094","volume":"58","author":"SP Schoenberger","year":"1998","unstructured":"Schoenberger, S. P. et al. Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC. Cancer. Res. 58, 3094\u20133100 (1998).","journal-title":"Cancer. Res."},{"key":"BFni0501423_CR28","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1093\/intimm\/6.3.369","volume":"6","author":"S Sanderson","year":"1994","unstructured":"Sanderson, S. & Shastri, N. LacZ inducible, antigen\/MHC-specific T cell hybrids. Int. Immunol. 6, 369\u2013376 (1994).","journal-title":"Int. Immunol."},{"key":"BFni0501423_CR29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","volume":"76","author":"KA Hogquist","year":"1994","unstructured":"Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17\u201327 (1994).","journal-title":"Cell"},{"key":"BFni0501423_CR30","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1046\/j.1440-1711.1999.00864.x","volume":"77","author":"AB Lyons","year":"1999","unstructured":"Lyons, A. B. Divided we stand: tracking cell proliferation with carboxyfluorescein diacetate succinimidyl ester. Immunol. Cell Biol. 77, 509\u2013515 (1999).","journal-title":"Immunol. Cell Biol."},{"key":"BFni0501423_CR31","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1126\/science.286.5441.952","volume":"286","author":"JF Huang","year":"1999","unstructured":"Huang, J. F. et al. TCR-Mediated internalization of peptide-MHC complexes acquired by T cells. Science 286, 952\u2013954 (1999).","journal-title":"Science"},{"key":"BFni0501423_CR32","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1084\/jem.191.7.1137","volume":"191","author":"I Hwang","year":"2000","unstructured":"Hwang, I. et al. T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen-presenting cells. J. Exp. Med. 191, 1137\u20131148 (2000).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/344065a0","volume":"344","author":"J Nikolic-Zugic","year":"1990","unstructured":"Nikolic-Zugic, J. & Bevan, M. J. Role of self-peptides in positively selecting the T-cell repertoire. Nature 344, 65\u201367 (1990).","journal-title":"Nature"},{"key":"BFni0501423_CR34","doi-asserted-by":"publisher","first-page":"23659","DOI":"10.1074\/jbc.274.33.23659","volume":"274","author":"N Bronstein-Sitton","year":"1999","unstructured":"Bronstein-Sitton, N., Wang, L., Cohen, L. & Baniyash, M. Expression of the T cell antigen receptor \u03b6 chain following activation is controlled at distinct checkpoints. Implications for cell surface receptor down-modulation and re-expression. J. Biol. Chem. 274, 23659\u201323665 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFni0501423_CR35","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S1074-7613(00)80169-7","volume":"12","author":"E San Jose","year":"2000","unstructured":"San Jose, E., Borroto, A., Niedergang, F., Alcover, A. & Alarcon, B. Triggering the TCR complex causes the downregulation of nonengaged receptors by a signal transduction-dependent mechanism. Immunity 12, 161\u2013170 (2000).","journal-title":"Immunity"},{"key":"BFni0501423_CR36","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.273.5271.104","volume":"273","author":"A Viola","year":"1996","unstructured":"Viola, A. & Lanzavecchia, A. T cell activation determined by T cell receptor number and tunable thresholds. Science 273, 104\u2013106 (1996).","journal-title":"Science"},{"key":"BFni0501423_CR37","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/0952-7915(91)90028-Y","volume":"3","author":"SL Swain","year":"1991","unstructured":"Swain, S. L. Lymphokines and the immune response: the central role of interleukin-2. Curr. Opin. Immunol. 3, 304\u2013310 (1991).","journal-title":"Curr. Opin. Immunol."},{"key":"BFni0501423_CR38","doi-asserted-by":"publisher","first-page":"5017","DOI":"10.4049\/jimmunol.165.9.5017","volume":"165","author":"DM Jelley-Gibbs","year":"2000","unstructured":"Jelley-Gibbs, D. M., Lepak, N. M., Yen, M. & Swain, S. L. Two distinct stages in the transition from naive CD4 T cells to effectors, early antigen-dependent and late cytokine-driven expansion and differentiation. J. Immunol. 165, 5017\u20135026 (2000).","journal-title":"J. Immunol."},{"key":"BFni0501423_CR39","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S1074-7613(00)80461-6","volume":"8","author":"G Iezzi","year":"1998","unstructured":"Iezzi, G., Karjalainen, K. & Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8, 89\u201395 (1998).","journal-title":"Immunity"},{"key":"BFni0501423_CR40","doi-asserted-by":"publisher","first-page":"3972","DOI":"10.1073\/pnas.88.9.3972","volume":"88","author":"J Karttunen","year":"1991","unstructured":"Karttunen, J. & Shastri, N. Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene. Proc. Natl Acad. Sci. USA 88. 3972\u20133976 (1991).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFni0501423_CR41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/76907","volume":"1","author":"H,U,W Veiga-Fernandes","year":"2000","unstructured":"Veiga-Fernandes, H., U., W., Bourgeois, C., McLean, A. & Rocha, B. Response of naive and memory CD8+ T cells to antigen stimulation in vivo. Nature Immunol. 1, 47\u201353 (2000).","journal-title":"Nature Immunol."},{"key":"BFni0501423_CR42","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1146\/annurev.immunol.18.1.829","volume":"18","author":"LM Staudt","year":"2000","unstructured":"Staudt, L. M. & Brown, P. O. Genomic views of the immune system. Annu. Rev. Immunol. 18, 829\u2013859 (2000).","journal-title":"Annu. Rev. Immunol."},{"key":"BFni0501423_CR43","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-4615-5355-7_14","volume":"452","author":"K Murali-Krishna","year":"1998","unstructured":"Murali-Krishna, K. et al. In vivo dynamics of anti-viral CD8 T cell responses to different epitopes. An evaluation of bystander activation in primary and secondary responses to viral infection. Adv. Exp. Med. Biol. 452, 123\u2013142 (1998).","journal-title":"Adv. Exp. Med. Biol."},{"key":"BFni0501423_CR44","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S1074-7613(00)80470-7","volume":"8","author":"K Murali-Krishna","year":"1998","unstructured":"Murali-Krishna, K. et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8, 177\u2013187 (1998).","journal-title":"Immunity"},{"key":"BFni0501423_CR45","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1084\/jem.186.2.239","volume":"186","author":"C Kurts","year":"1997","unstructured":"Kurts, C., Kosaka, H., Carbone, F. R., Miller, J. F. A. P. & Heath, W. R. Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8+ T cells. J. Exp. Med. 186, 239\u2013245 (1997).","journal-title":"J. Exp. Med."},{"key":"BFni0501423_CR46","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0165-2478(88)90178-2","volume":"18","author":"J Zhang","year":"1988","unstructured":"Zhang, J., MacLennan, I. C., Liu, Y. J. & Lane, P. J. Is rapid proliferation in B centroblasts linked to somatic mutation in memory B cell clones? Immunol. Lett. 18, 297\u2013299 (1988).","journal-title":"Immunol. Lett."},{"key":"BFni0501423_CR47","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0022-1759(91)90325-A","volume":"145","author":"P Matzinger","year":"1991","unstructured":"Matzinger, P. The JAM test. A simple assay for DNA fragmentation and cell death. J. Immunol. Meth. 145, 185\u2013192 (1991).","journal-title":"J. Immunol. Meth."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ni0501_423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ni0501_423","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ni0501_423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:22:07Z","timestamp":1684448527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ni0501_423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,5]]}},"alternative-id":["BFni0501423"],"URL":"https:\/\/doi.org\/10.1038\/87730","relation":{},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5]]}}}