{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:45:45Z","timestamp":1774068345978,"version":"3.50.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"content-version":"tdm","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":[[2001,8]]},"DOI":"10.1038\/90650","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T04:32:48Z","timestamp":1027657968000},"page":"711-717","source":"Crossref","is-referenced-by-count":270,"title":["Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR"],"prefix":"10.1038","volume":"2","author":[{"given":"Mark K.","family":"Slifka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Lindsay","family":"Whitton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"BFni0801_711_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0065-3233(08)60487-8","volume":"49","author":"HN Eisen","year":"1996","unstructured":"Eisen, H. N., Sykulev, Y. & Tsomides, T. J. Antigen-specific T-cell receptors and their reactions with complexes formed by peptides with major histocompatibility complex proteins. Adv. Protein Chem. 49, 1\u201356 (1996).","journal-title":"Adv. Protein Chem."},{"key":"BFni0801_711_CR2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0167-5699(97)80027-8","volume":"18","author":"S Valitutti","year":"1997","unstructured":"Valitutti, S. & Lanzavecchia, A. Serial triggering of TCRs: a basis for the sensitivity and specificity of antigen recognition. Immunol. Today 18, 299\u2013304 (1997).","journal-title":"Immunol. Today"},{"key":"BFni0801_711_CR3","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1084\/jem.189.4.701","volume":"189","author":"DH Busch","year":"1999","unstructured":"Busch, D. H. & Pamer, E. G. T cell affinity maturation by selective expansion during infection. J. Exp. Med. 189, 701\u2013710 (1999).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR4","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S1074-7613(00)80048-5","volume":"10","author":"PA Savage","year":"1999","unstructured":"Savage, P. A., Boniface, J. J. & Davis, M. M. A kinetic basis for T cell receptor repertoire selection during an immune response. Immunity 10, 485\u2013492 (1999).","journal-title":"Immunity"},{"key":"BFni0801_711_CR5","doi-asserted-by":"publisher","first-page":"11990","DOI":"10.1073\/pnas.92.26.11990","volume":"92","author":"Y Sykulev","year":"1995","unstructured":"Sykulev, Y., Cohen, R. J. & Eisen, H. N. The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes. Proc. Natl Acad. Sci. USA 92, 11990\u201311992 (1995).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFni0801_711_CR6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0161-5890(98)00020-0","volume":"35","author":"M Salzmann","year":"1998","unstructured":"Salzmann, M. & Bachmann, M. F. Estimation of maximal affinities between T-cell receptors and MHC\/peptide complexes. Mol. Immunol. 35, 65\u201371 (1998).","journal-title":"Mol. Immunol."},{"key":"BFni0801_711_CR7","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/248701a0","volume":"248","author":"RM Zinkernagel","year":"1974","unstructured":"Zinkernagel, R. M. & Doherty, P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248, 701\u2013702 (1974).","journal-title":"Nature"},{"key":"BFni0801_711_CR8","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/oxfordjournals.bmb.a072029","volume":"41","author":"MBA Oldstone","year":"1985","unstructured":"Oldstone, M. B. A. et al. Virus and immune responses: lymphocytic choriomeningitis virus as a prototype model of viral pathogenesis. Br. Med. Bull. 41, 70\u201374 (1985).","journal-title":"Br. Med. Bull."},{"key":"BFni0801_711_CR9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1126\/science.272.5258.54","volume":"272","author":"R Ahmed","year":"1996","unstructured":"Ahmed, R. & Gray, D. Immunological memory and protective immunity: understanding their relation. Science 272, 54\u201360 (1996).","journal-title":"Science"},{"key":"BFni0801_711_CR10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S1074-7613(00)80197-1","volume":"12","author":"MK Slifka","year":"2000","unstructured":"Slifka, M. K. & Whitton, J. L. Antigen-specific regulation of T cell-mediated cytokine production. Immunity 12, 451\u2013457 (2000).","journal-title":"Immunity"},{"key":"BFni0801_711_CR11","first-page":"575","volume-title":"Persistent Viral Infections","author":"MJ Buchmeier","year":"1999","unstructured":"Buchmeier, M. J. & Zajac, A. in Persistent Viral Infections (eds Ahmed, R. & Chen, I.) 575\u2013605 (John Wiley & Sons, New York, 1999)."},{"key":"BFni0801_711_CR12","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":"BFni0801_711_CR13","first-page":"257","volume":"1","author":"JL Whitton","year":"1990","unstructured":"Whitton, J. L. Lymphocytic choriomeningitis virus CTL. Semin. Virol. 1, 257\u2013262 (1990).","journal-title":"Semin. Virol."},{"key":"BFni0801_711_CR14","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1084\/jem.183.4.1917","volume":"183","author":"S Valitutti","year":"1996","unstructured":"Valitutti, S., Muller, S., Dessing, M. & Lanzavecchia, A. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J. Exp. Med. 183, 1917\u20131921 (1996).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR15","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1084\/jem.189.10.1521","volume":"189","author":"MF Bachmann","year":"1999","unstructured":"Bachmann, M. F. et al. Developmental regulation of lck targeting to the CD8 coreceptor controls signaling in na\u00efve and memory T cells. J. Exp. Med. 189, 1521\u20131530 (1999).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR16","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.1600-065X.1982.tb01062.x","volume":"68","author":"E Nakayama","year":"1982","unstructured":"Nakayama, E. Blocking of effector cell cytotoxicity and T-cell proliferation by Lyt antisera. Immunol. Rev. 68, 117\u2013134 (1982).","journal-title":"Immunol. Rev."},{"key":"BFni0801_711_CR17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1600-065X.1982.tb01059.x","volume":"68","author":"N Hollander","year":"1982","unstructured":"Hollander, N. Effects of anti-Lyt antibodies on T-cell functions. Immunol. Rev. 68, 43\u201366 (1982).","journal-title":"Immunol. Rev."},{"key":"BFni0801_711_CR18","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/1074-7613(94)90101-5","volume":"1","author":"MG von Herrath","year":"1994","unstructured":"von Herrath, M. G., Dockter, J. & Oldstone, M. B. A. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1, 231\u2013242 (1994).","journal-title":"Immunity"},{"key":"BFni0801_711_CR19","doi-asserted-by":"publisher","first-page":"208","DOI":"10.4049\/jimmunol.164.1.208","volume":"164","author":"MK Slifka","year":"2000","unstructured":"Slifka, M. K. & Whitton, J. L. Activated and memory CD8+ T cells can be distinguished by their cytokine profiles and phenotypic markers. J. Immunol. 164, 208\u2013216 (2000).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR20","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S1074-7613(00)80572-5","volume":"8","author":"F Crawford","year":"1998","unstructured":"Crawford, F. et al. Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes. Immunity 8, 675\u2013682 (1998).","journal-title":"Immunity"},{"key":"BFni0801_711_CR21","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.4049\/jimmunol.162.4.2227","volume":"162","author":"C Yee","year":"1999","unstructured":"Yee, C. et al. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J. Immunol. 162, 2227\u20132234 (1999).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR22","doi-asserted-by":"publisher","first-page":"191","DOI":"10.4049\/jimmunol.164.1.191","volume":"164","author":"CT Nugent","year":"2000","unstructured":"Nugent, C. T. et al. Characterization of CD8+ T lymphocytes that persist after peripheral tolerance to a self antigen expressed in the pancreas. J. Immunol. 164, 191\u2013200 (2000).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR23","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1084\/jem.191.2.335","volume":"191","author":"MA Daniels","year":"2000","unstructured":"Daniels, M. A. & Jameson, S. C. Critical role for CD8 in T cell receptor binding and activation by peptide\/major histocompatibility complex multimers. J. Exp. Med. 191, 335\u2013346 (2000).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR24","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.4049\/jimmunol.163.8.4342","volume":"163","author":"JA Whelan","year":"1999","unstructured":"Whelan, J. A. et al. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent. J. Immunol. 163, 4342\u20134348 (1999).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR25","doi-asserted-by":"publisher","first-page":"6994","DOI":"10.4049\/jimmunol.165.12.6994","volume":"165","author":"S Reichstetter","year":"2000","unstructured":"Reichstetter, S. et al. Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response. J. Immunol. 165, 6994\u20136998 (2000).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR26","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1084\/jem.188.1.71","volume":"188","author":"DJ Sourdive","year":"1998","unstructured":"Sourdive, D. J. et al. Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infection. J. Exp. Med. 188, 71\u201382 (1998).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR27","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1084\/jem.188.11.1993","volume":"188","author":"MY Lin","year":"1998","unstructured":"Lin, M. Y. & Welsh, R. M. Stability and diversity of T cell receptor repertoire usage during lymphocytic choriomeningitis virus infection of mice. J. Exp. Med. 188, 1993\u20132005 (1998).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/342559a0","volume":"342","author":"H Pircher","year":"1989","unstructured":"Pircher, H. et al. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342, 559\u2013561 (1989).","journal-title":"Nature"},{"key":"BFni0801_711_CR29","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1084\/jem.188.1.103","volume":"188","author":"DR Fitzpatrick","year":"1998","unstructured":"Fitzpatrick, D. R. et al. Distinct methylation of the interferon gamma (IFN-\u03b3) and interleukin 3 (IL-3) genes in newly activated primary CD8+ T lymphocytes: regional IFN-\u03b3 promoter demethylation and mRNA expression are heritable in CD44hiCD8+ T cells. J. Exp. Med. 188, 103\u2013117 (1998).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR30","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S1074-7613(00)80642-1","volume":"9","author":"S Agarwal","year":"1998","unstructured":"Agarwal, S. & Rao, A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765\u2013775 (1998).","journal-title":"Immunity"},{"key":"BFni0801_711_CR31","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.4049\/jimmunol.161.10.5338","volume":"161","author":"S Oehen","year":"1998","unstructured":"Oehen, S. & Brduscha-Riem, K. Differentiation of na\u00efve CTL to effector and memory CTL: correlation of effector function with phenotype and cell division. J. Immunol. 161, 5338\u20135346 (1998).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR32","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1006\/smvy.1994.1035","volume":"5","author":"R Ahmed","year":"1994","unstructured":"Ahmed, R. Virus persistence and immune memory. Semin. Virol. 5, 319\u2013324 (1994).","journal-title":"Semin. Virol."},{"key":"BFni0801_711_CR33","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S1074-7613(00)80376-3","volume":"7","author":"MF Bachmann","year":"1997","unstructured":"Bachmann, M. F. et al. Distinct roles for LFA-1 and CD28 during activation of na\u00efve T cells: adhesion versus costimulation. Immunity 7, 549\u2013557 (1997).","journal-title":"Immunity"},{"key":"BFni0801_711_CR34","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1084\/jem.190.10.1383","volume":"190","author":"MF Bachmann","year":"1999","unstructured":"Bachmann, M. F., Barner, M. & Kopf, M. CD2 sets quantitative thresholds in T cell activation. J. Exp. Med. 190, 1383\u20131392 (1999).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR35","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1084\/jem.191.7.1241","volume":"191","author":"LE Harrington","year":"2000","unstructured":"Harrington, L. E. et al. Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. J. Exp. Med. 191, 1241\u20131246 (2000).","journal-title":"J. Exp. Med."},{"key":"BFni0801_711_CR36","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.4049\/jimmunol.164.4.2009","volume":"164","author":"MK Slifka","year":"2000","unstructured":"Slifka, M. K., Pagarigan, R. R. & Whitton, J. L. NK markers are expressed on a high percentage of virus-specific CD8+ and CD4+ T cells. J. Immunol. 164, 2009\u20132015 (2000).","journal-title":"J. Immunol."},{"key":"BFni0801_711_CR37","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/0092-8674(94)90334-4","volume":"76","author":"A Weiss","year":"1994","unstructured":"Weiss, A. & Littman, D. R. Signal transduction by lymphocyte antigen receptors. Cell 76, 263\u2013274 (1994).","journal-title":"Cell"},{"key":"BFni0801_711_CR38","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/S0952-7915(96)80130-0","volume":"8","author":"AC Chan","year":"1996","unstructured":"Chan, A. C. & Shaw, A. S. Regulation of antigen receptor signal transduction by protein tyrosine kinases. Curr. Opin. Immunol. 8, 394\u2013401 (1996).","journal-title":"Curr. Opin. Immunol."},{"key":"BFni0801_711_CR39","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S1074-7613(00)80315-5","volume":"5","author":"RL Wange","year":"1996","unstructured":"Wange, R. L. & Samelson, L. E. Complex complexes: signaling at the TCR. Immunity 5, 197\u2013205 (1996).","journal-title":"Immunity"},{"key":"BFni0801_711_CR40","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1128\/JVI.68.1.352-357.1994","volume":"68","author":"MS Horwitz","year":"1994","unstructured":"Horwitz, M. S., Yanagi, Y. & Oldstone, M. B. A. T-cell receptors from virus-specific cytotoxic T lymphocytes recognizing a single immunodominant nine-amino-acid viral epitope show marked diversity. J. Virol. 68, 352\u2013357 (1994).","journal-title":"J. Virol."},{"key":"BFni0801_711_CR41","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/S0952-7915(00)00085-6","volume":"12","author":"PS Myung","year":"2000","unstructured":"Myung, P. S., Boerthe, N. J. & Koretzky, G. A. Adapter proteins in lymphocyte antigen-receptor signaling. Curr. Opin. Immunol. 12, 256\u2013266 (2000).","journal-title":"Curr. Opin. Immunol."},{"key":"BFni0801_711_CR42","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1006\/smim.2000.0205","volume":"12","author":"W Zhang","year":"2000","unstructured":"Zhang, W. & Samelson, L. E. The role of membrane-associated adaptors in T cell receptor signalling. Semin. Immunol. 12, 35\u201341 (2000).","journal-title":"Semin. Immunol."},{"key":"BFni0801_711_CR43","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/S0952-7915(00)00083-2","volume":"12","author":"LP Kane","year":"2000","unstructured":"Kane, L. P., Lin, J. & Weiss, A. Signal transduction by the TCR for antigen. Curr. Opin. Immunol. 12, 242\u2013249 (2000).","journal-title":"Curr. Opin. Immunol."},{"key":"BFni0801_711_CR44","first-page":"135","volume":"14","author":"TM Fahmy","year":"2001","unstructured":"Fahmy, T. M., Bieler, J. G., Edidin, M. & Schneck, J. P. Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen. Immunity 14, 135\u2013143 (2001).","journal-title":"Immunity"},{"key":"BFni0801_711_CR45","doi-asserted-by":"publisher","first-page":"5387","DOI":"10.1073\/pnas.080078297","volume":"97","author":"PD Holler","year":"2000","unstructured":"Holler, P. D. et al. In vitro evolution of a T cell receptor with high affinity for peptide\/MHC. Proc. Natl Acad. Sci. USA 97, 5387\u20135392 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFni0801_711_CR46","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1084\/jem.184.2.485","volume":"184","author":"MA Alexander-Miller","year":"1996","unstructured":"Alexander-Miller, M. A., Leggatt, G. R., Sarin, A. & Berzofsky, J. A. Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL. J. Exp. Med. 184, 485\u2013492 (1996).","journal-title":"J. Exp. Med."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ni0801_711.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ni0801_711","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ni0801_711.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:28:47Z","timestamp":1684434527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ni0801_711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["BFni0801_711"],"URL":"https:\/\/doi.org\/10.1038\/90650","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1000515.8806","asserted-by":"object"}]},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}