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MHC class Ia–restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)–restricted memory response

Nature Immunology volume 5, pages 159–168 (2004)Cite this article

Abstract

Listeria monocytogenes infection generates major histocompatibility complex (MHC) class Ia–restricted and MHC class Ib-(H2-M3)–restricted effector and memory CD8+ T cells. However, only MHC class Ia–restricted memory cells expand after rechallenge, and it is unknown if MHC class Ib–restricted memory CD8+ T cells generated by vaccination are protective. We show here that H2-M3-restricted memory CD8+ T cells were capable of secondary expansion but, in contrast to primary H2-M3-restricted effector cells, failed to provide protective immunity. In lm-immune mice, MHC class Ia–restricted memory CD8+ T cells prevented the expansion of H2-M3-restricted memory T cell populations by limiting dendritic cell antigen presentation. Thus, protective immunity by H2-M3-resricted T cells is limited to primary infection, indicating that memory MHC class Ia–restricted T cells prevent nonessential immune responses during secondary infection.

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Figure 1: Priming of f-MIGWII-specific CD8+ T cells after listeria infection or immunization with peptide-coated DCs.
Figure 2: Differential protection by f-MIGWII-specific primary effector and memory CD8+ T cells.
Figure 3: Secondary effectors specific for f-MIGWII are deficient in rapid cytolysis and mainly use the CD95L-CD95 pathway.
Figure 4: Memory cell populations specific for f-MIGWII generated by listeria infection are capable of secondary expansion.
Figure 5: Regulation of MHC class Ib–restricted memory cell expansion is perforin independent.
Figure 6: Differential APC requirements for proliferation of LLO(91–99)-specific and f-MIGWII-specific memory CD8+ T cells.
Figure 7: MHC class Ia–restricted memory CD8+ T cells limit DC presentation of listeria antigens in immune mice.

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Acknowledgements

We thank K. Rensberger and R. Podyminogin for technical assistance; E. Pamer (Memorial Sloan Kettering, New York, New York) for TCR-transgenic mice; C.-R. Wang (University of Chicago, Chicago, Illinois) for H2-M3-specific antibody; and S. Perlman (University of Iowa, Iowa City, Iowa) for critical review of the manuscript. We also thank the National Institute of Allergy and Infectious Disease tetramer core facility for reagents. Supported by National Institutes of Health grants AI42767, AI46653, AI50073 (J.T.H.), T32AI07511 (S.E.H.), T32AI07485 (B.B.P.) and T32AI07260 (K.A.N.M.), and a Leukemia and Lymphoma Society Fellow Grant (V.P.B.).

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Authors and Affiliations

  1. Interdisciplinary Program in Immunology, The University of Iowa, Iowa City, 52242, Iowa, USA

    Sara E Hamilton, Brandon B Porter & John T Harty

  2. Department of Microbiology, The University of Iowa, Iowa City, 52242, Iowa, USA

    Kelly A Nordyke Messingham, Vladimir P Badovinac & John T Harty

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Correspondence to John T Harty.

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Hamilton, S., Porter, B., Messingham, K. et al. MHC class Ia–restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)–restricted memory response. Nat Immunol 5, 159–168 (2004). https://doi.org/10.1038/ni1026

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