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Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen

Nature volume 398, pages 77–80 (1999)Cite this article

Abstract

Cytotoxic T lymphocytes (CTLs) are thought to detect viral infections by monitoring the surface of all cells for the presence of viral peptides bound to major histocompatibility complex (MHC) class I molecules. In most cells, peptides presented by MHC class I molecules are derived exclusively from proteins synthesized by the antigen-bearing cells1. Macrophages and dendritic cells also have an alternative MHC class I pathway that can present peptides derived from extracellular antigens; however, the physiological role of this process is unclear2. Here we show that virally infected non-haematopoietic cells are unable to stimulate primary CTL-mediated immunity directly. Instead, bone-marrow-derived cells are required as antigen-presenting cells (APCs) to initiate anti-viral CTL responses. In these APCs, the alternative (exogenous) MHC class I pathway is the obligatory mechanism for the initiation of CTL responses to viruses that infect only non-haematopoietic cells.

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Figure 1: CTL responses to wild-type vaccinia virus and OVA in recombinant vaccinia virus requires a bone-marrow-derived APC.
Figure 2: TAP0/0 → B6 mice can generate CTL responses comparable to those in B6 → B6 mice when immunized with APCs loaded with antigenic peptide.
Figure 3: TAP0/0 → B6 mice can generate MHC class II-restricted responses comparable to those in B6 → B6 mice.
Figure 4: Initiation of the CTL response to polio–OVA requires the presence of bone-marrow-derived APCs, but not their infection.

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Acknowledgements

We thank R. O. Donis and the members of the Rock laboratory for helpful discussions; R. Welsh, L. Berg, G. Soldevila and N. Kisaiti for critical reading of the manuscript; W.Yong Zang and L. Rothstein for technical assistance; and M. Bevan for EG7 cells, P. Doherty for MC57G cells, and J. Yewdell for vaccinia-OVA and vaccinia SS-SIINFEKL. This work was supported by NIH grants to K.L.R. and R.A. L.J.S. was supported by an NIH Research Training Grant.

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Authors and Affiliations

  1. Department of Pathology, University of Massachusetts Medical Center, Worcester, 01655-0118, Massachusetts, USA

    Luis J. Sigal & Kenneth L. Rock

  2. Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, 94143-0414, California, USA

    Shane Crotty & Raul Andino

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Correspondence to Kenneth L. Rock.

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Sigal, L., Crotty, S., Andino, R. et al. Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature 398, 77–80 (1999). https://doi.org/10.1038/18038

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