{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:13:32Z","timestamp":1791296012688,"version":"4.1.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,16]]},"abstract":"<jats:p>Bone marrow (BM)-derived professional antigen-presenting cells (pAPCs) are required for the generation of cytotoxic T lymphocyte (CTL) responses to vaccinia virus and poliovirus. Furthermore, these BM-derived pAPCs require a functional transporter associated with antigen presentation (TAP). In this report we analyze the requirements for BM-derived pAPCs and TAP in the initiation of CTL responses to lymphocytic choriomeningitis virus (LCMV) and influenza virus (Flu). Our results indicate a requirement for BM-derived pAPCs for the CTL responses to these viruses. However, we found that the generation of CTLs to one LCMV epitope (LCMV nucleoprotein 396\u2013404) was dependent on BM-derived pAPCs but, surprisingly, TAP independent. The study of the CTL response to Flu confirmed the existence of this BM-derived pAPC-dependent\/TAP-independent CTL response and indicated that the TAP-independent pathway is \u223c10\u2013300-fold less efficient than the TAP-dependent pathway.<\/jats:p>","DOI":"10.1084\/jem.192.8.1143","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1143-1150","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Bone Marrow\u2013Derived Antigen-Presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (Tap)-Dependent and -Independent Pathways of Antigen Presentation"],"prefix":"10.1084","volume":"192","author":[{"given":"Luis J.","family":"Sigal","sequence":"first","affiliation":[{"name":"aDepartment of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Rock","sequence":"additional","affiliation":[{"name":"aDepartment of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,10,16]]},"reference":[{"key":"2023072509274357200_R1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.iy.07.040189.003125","article-title":"Antigen recognition by class I-restricted T lymphocytes","volume":"7","author":"Townsend","year":"1989","journal-title":"Annu. 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Virol."},{"key":"2023072509274357200_R13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S1074-7613(00)80470-7","article-title":"Counting antigen-specific CD8 T cellsa reevaluation of bystander activation during viral infection","volume":"8","author":"Murali-Krishna","year":"1998","journal-title":"Immunity."},{"key":"2023072509274357200_R14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1074-7613(00)80308-8","article-title":"Duration of TCR stimulation determines costimulatory requirement of T cells","volume":"5","author":"Kundig","year":"1996","journal-title":"Immunity."},{"key":"2023072509274357200_R15","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1074-7613(00)80248-4","article-title":"In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter","volume":"4","author":"Huang","year":"1996","journal-title":"Immunity."},{"key":"2023072509274357200_R16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1084\/jem.177.2.367","article-title":"Tolerance of CD8+ T cells developing in parent\u2192F1 chimeras prepared with supralethal irradiationstep-wise induction of tolerance in the intrathymic and extrathymic environments","volume":"177","author":"Kosaka","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072509274357200_R17","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1084\/jem.171.4.1101","article-title":"Strong T cell tolerance in parent\u2192F1 bone marrow chimeras prepared with supralethal irradiation. Evidence for clonal deletion and anergy","volume":"171","author":"Gao","year":"1990","journal-title":"J. Exp. Med."},{"key":"2023072509274357200_R18","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.4049\/jimmunol.137.6.1764","article-title":"T cell specificity in twice-irradiated F1\u2192parent bone marrow chimerasfailure to detect a role for immigrant marrow-derived cells in imprinting intrathymic H-2 restriction","volume":"137","author":"Ron","year":"1986","journal-title":"J. Immunol."},{"key":"2023072509274357200_R19","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1126\/science.7513904","article-title":"Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens","volume":"264","author":"Huang","year":"1994","journal-title":"Science."},{"key":"2023072509274357200_R20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4049\/jimmunol.159.1.11","article-title":"The dominant role of bone marrow-derived cells in CTL induction following plasmid DNA immunization at different sites","volume":"159","author":"Iwasaki","year":"1997","journal-title":"J. Immunol."},{"key":"2023072509274357200_R21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/jlb.66.2.350","article-title":"Dendritic cells in genetic immunization","volume":"66","author":"Takashima","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"2023072509274357200_R22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1084\/jem.189.1.169","article-title":"DNA vaccinationtransfection and activation of dendritic cells as key events for immunity","volume":"189","author":"Akbari","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509274357200_R23","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1084\/jem.188.6.1075","article-title":"Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization","volume":"188","author":"Porgador","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509274357200_R24","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.4049\/jimmunol.160.12.5707","article-title":"Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages\/antigen-presenting cells","volume":"160","author":"Chattergoon","year":"1998","journal-title":"J. Immunol."},{"key":"2023072509274357200_R25","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nm1096-1122","article-title":"DNA-based immunization by in vivo transfection of dendritic cells","volume":"2","author":"Condon","year":"1996","journal-title":"Nat. Med."},{"key":"2023072509274357200_R26","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1084\/jem.192.8.1135","article-title":"Requirements for bone marrow\u2013derived antigen presenting cells in priming cytotoxic T cell responses to intracellular pathogens","volume":"192","author":"Lenz","year":"2000","journal-title":"J. Exp. Med"},{"key":"2023072509274357200_R27","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0090-1229(80)90067-7","article-title":"Lymphohemopoietic origin of the immunogenic, virus-antigen-presenting cells triggering anti-viral T-cell responses","volume":"15","author":"Zinkernagel","year":"1980","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2023072509274357200_R28","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1084\/jem.186.7.1087","article-title":"Two novel routes of transporter associated with antigen processing (TAP)-independent major histocompatibility complex class I antigen processing","volume":"186","author":"Snyder","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509274357200_R29","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1084\/jem.182.5.1615","article-title":"Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein","volume":"182","author":"Hombach","year":"1995","journal-title":"J. Exp. 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