Bone Marrow-derived 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

doi:10.1084/jem.192.8.1143

Published online 16 October 2000.

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© The Rockefeller University Press, 0022-1007/2000/10/1143/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 8, October 16, 2000 1143-1150

Original Article

Bone Marrow–derived 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

Luis J. Sigal^a and Kenneth L. Rock^a
^a Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Correspondence to: Luis J. Sigal, Fox Chase Cancer Center, Rm. 343, 7701 Burholme Ave., Philadelphia, PA 19111. Tel:215-728-7061 Fax:413-487-5406

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 associatedwith antigen presentation (TAP). In this report we analyze therequirements for BM-derived pAPCs and TAP in the initiationof CTL responses to lymphocytic choriomeningitis virus (LCMV)and influenza virus (Flu). Our results indicate a requirementfor BM-derived pAPCs for the CTL responses to these viruses.However, we found that the generation of CTLs to one LCMV epitope(LCMV nucleoprotein 396–404) was dependent on BM-derivedpAPCs but, surprisingly, TAP independent. The study of the CTLresponse to Flu confirmed the existence of this BM-derived pAPC-dependent/TAP-independentCTL response and indicated that the TAP-independent pathwayis $~$ 10–300-fold less efficient than the TAP-dependent pathway.

Key Words: mice, lymphocytic choriomeningitis virus, influenza virus, Tlymphocytes, cytotoxic, immunity, cellular

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