H-2M3 presents a listeria monocytogenes peptide to cytotoxic T lymphocytes

Pamer, Eric G.; Wang, Chyung Ru; Flaherty, Lorraine; Lindahl, Kirsten Fischer; Bevan, Michael J.

doi:10.1016/0092-8674(92)90097-v

Cited by 190 publications

(131 citation statements)

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“…Thus, FPR might play a more important role than FPRL1 and FPRL2 in host defense against microbial infection. The mouse MHC class Ib antigen-presenting molecule, H2-M3, also has a preferential requirement for Nformylated ligands, and presents N-formylated peptides derived from pathogenic organisms to cytolytic T lymphocytes, which mediate both specific clearance of primary infections and memory immune responses [26][27][28]. A number of N-formylated peptides identified as ligands of H2-M3, originating from L. monocytogenes [29][30][31] and from the N terminus of mouse mitochondrial proteins [32], have been shown to be chemotactic and to activate rabbit neutrophils in vitro [23].…”

Section: Discussionmentioning

confidence: 99%

Human mitochondria-derivedN-formylated peptides are novel agonists equally active on FPR and FPRL1, whileListeria monocytogenes-derived peptides preferentially activate FPR

2005

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N-formyl peptides are cleavage products of bacterial and mitochondrial proteins, and can attract leukocytes to sites of infection or tissue damage. In this study, HL-60 cell lines expressing the human N-formyl peptide receptor FPR or its two homologues (FPRL1, FPRL2) were used to determine the receptor selectivity of N-formylated peptides derived from Listeria monocytogenes or from human mitochondrial proteins. Bacterial peptides were 100-fold more potent on FPR than on FPRL1, whereas none of them could trigger intracellular signaling through FPRL2. In contrast, N-formylated hexapeptides corresponding to the N terminus of mitochondrial NADH dehydrogenase subunits 4 (fMLKLIV) and 6 (fMMYALF), and cytochrome c oxidase subunit I (fMFADRW) were equally potent on FPR and FPRL1. They triggered cellular responses with the following order of potency: fMMYALF > fMLKLIV > fMFADRW, with an EC 50 , in a Fura-2 calcium mobilization assay, of 10 nM, 44 nM, and 160 nM on FPRexpressing cells, and 15 nM, 55 nM and 120 nM on FPRL1-expressing cells. fMMYALF was also a low-affinity agonist of FPRL2 (EC 50 of 1 lM) and was chemotactic for both FPRL1-and FPRL2-expressing cells. We identified novel mitochondrial host-derived agonists for human N-formyl-peptide receptors that might play a role in inflammatory or degenerative processes linked to their stimulation.

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Section: Discussionmentioning

confidence: 99%

Human mitochondria-derivedN-formylated peptides are novel agonists equally active on FPR and FPRL1, whileListeria monocytogenes-derived peptides preferentially activate FPR

2005

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“…An explanation for this MHC-unrestricted recognition was provided when H2-M3 was shown to present L. monocytogenes-derived peptides to CD8 ϩ T cells (17,18); three Listeria-derived N-formyl epitopes have since been identified (7,19,20). We recently demonstrated that H2-M3-restricted T cells specific for the Listeria-derived peptide fMIGWIIA expand earlier than MHC class Ia-restricted T cells in response to primary infection, but fail to expand substantially upon reinfection with L. monocytogenes (21).…”

Section: Variable Immunodominance Hierarchies For H2-m3-restrictedmentioning

confidence: 99%

Variable Immunodominance Hierarchies for H2-M3-RestrictedN-Formyl Peptides Following Bacterial Infection

Kerksiek

Busch

Pamer

2001

The Journal of Immunology

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H2-M3-restricted presentation of N-formyl methionine (f-Met) peptides to CD8+ T cells provides a mechanism for selective recognition of bacterial infection. In this report we demonstrate that Listeria monocytogenes infection induces distinct CD8+ T cell populations specific for each of the known Listeria-derived formyl methionine peptides presented by M3. The sum H2-M3-restricted, Listeria-specific T cell response constitutes a major fraction of the total CD8+ T cell response to primary infection. H2-M3-restricted T cell populations expand synchronously in vivo and achieve peak frequencies ∼2 days earlier than MHC class Ia-restricted T cell populations. Although cross-recognition of different f-Met peptides by M3-restricted T cells was previously described, costaining of CD8+ T cells ex vivo with H2-M3 tetramers complexed with different f-Met peptides shows that the majority of Listeria-specific, M3-restricted CD8+ T cells are peptide specific. In contrast to the highly predictable size and immunodominance hierarchies of MHC class Ia-restricted T cell responses, the magnitudes of T cell responses specific for H2-M3-restricted peptides are remarkably variable between genetically identical mice. Our findings demonstrate that H2-M3-restricted T cell responses are distinct from classically restricted T cell responses to bacterial infection.

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“…Bacterial supernatant preparation (14) L. monocytogenes 10403s and the fMIGWII epitope-deficient strain (fMIG neg ) were grown overnight in 5 ml BHI medium. Ten liters of modified Welshimers' Broth (MWB) peptide-free minimal medium (28) were inoculated with 500 l of the bacterial overnight cultures and incubated at 37°C without agitation.…”

Section: Synthetic Peptidesmentioning

confidence: 99%

“…Several peptides derived from Mycobacterium tuberculosis, for example, can be bound by H2-M3 and presented to CD8 ϩ T cells (10). In the setting of murine infection with Listeria monocytogenes, three H2-M3-restricted peptides, fMIGWII (11), fMIVIL (Fr38) (12), and fMIVTLF (13), have been identified (11,14). Although most recent studies have demonstrated peptide presentation, one study suggested that bacterial glycolipids may be presented by H2-M3 to L. monocytogenes-specific CD8 ϩ T cells (15).…”

mentioning

confidence: 99%

Promiscuity of MHC Class Ib-Restricted T Cell Responses

Ploß

Lauvau

Contos

et al. 2003

The Journal of Immunology

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Murine infection with the Gram-positive intracellular bacterium Listeria monocytogenes activates CD8+ T cells that recognize bacterially derived N-formyl methionine peptides in the context of H2-M3 MHC class Ib molecules. Three peptides, fMIGWII, fMIVIL, and fMIVTLF, are targets of L. monocytogenes-specific CD8+ T cells. To investigate epitope cross-recognition by H2-M3-restricted CD8+ T cells, we deleted the sequence encoding fMIGWII from a virulent strain of L. monocytogenes. Infection with fMIGWII-deficient L. monocytogenes unexpectedly primed CD8+ T cells that stain with fMIGWII/H2-M3 tetramers and lyse fMIGWII-coated target cells in vivo. Because the fMIGWII sequence is nonredundant, we speculated that other bacterially derived Ags are priming these responses. HPLC peptide fractionation of bacterial culture supernatants revealed several distinct L. monocytogenes-derived peptides that are recognized by fMIGWII-specific T cells. Our results demonstrate that the dominant H2-M3-restricted CD8+ T cell population, although reactive with fMIGWII, is primed by other, non-fMIGWII peptides derived from L. monocytogenes. Although this degree of Ag receptor promiscuity is unusual for the adaptive immune system, it may be a more common feature of T cell responses restricted by nonpolymorphic MHC class Ib molecules.

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H-2M3 presents a listeria monocytogenes peptide to cytotoxic T lymphocytes

Cited by 190 publications

References 50 publications

Human mitochondria-derivedN-formylated peptides are novel agonists equally active on FPR and FPRL1, whileListeria monocytogenes-derived peptides preferentially activate FPR

Human mitochondria-derivedN-formylated peptides are novel agonists equally active on FPR and FPRL1, whileListeria monocytogenes-derived peptides preferentially activate FPR

Variable Immunodominance Hierarchies for H2-M3-RestrictedN-Formyl Peptides Following Bacterial Infection

Promiscuity of MHC Class Ib-Restricted T Cell Responses

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