Variable Immunodominance Hierarchies for H2-M3-Restricted<i>N</i>-Formyl Peptides Following Bacterial Infection

Kerksiek, Kristen M.; Busch, Dirk H.; Pamer, Eric G.

doi:10.4049/jimmunol.166.2.1132

Cited by 17 publications

(21 citation statements)

References 35 publications

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“…For example, H2-M3-restricted CD8 T cells can play an important role in the clearance of Listeria monocytogenes (LM) 3 infection (22,(25)(26)(27)(28). H2-M3-restricted CD8 ϩ cells have also been found in Mycobacteria tuberculosis-infected mice (29,30).…”

Section: Thymus-dependent Memory Phenotype Cd8 T Cells Inmentioning

confidence: 99%

Thymus-Dependent Memory Phenotype CD8 T Cells in Naive B6.H-2Kb−/−Db−/− Animals Mediate an Antigen-Specific Response against Listeria monocytogenes

Berg

Murray

et al. 2005

The Journal of Immunology

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B6.H-2Kb−/−Db−/− (DKO) mice have greatly reduced numbers of mature CD8αβ T cells in their periphery. However, these non-class Ia-selected CD8αβ T cells are able to mediate immune responses to a number of pathogens. Approximately 60% of the CD8αβ T cells in the spleen and peripheral lymph nodes of naive DKO mice display a memory (CD44high) phenotype. To investigate the origins of these non-class Ia-selected CD8αβCD44high cells, we traced the phenotype of recent thymic emigrants and found that most were CD44low. We also determined whether their appearance was thymus dependent and found that only a small percentage of non-class Ia-selected CD8αβCD44high cells develop in a thymus-independent pathway. Functionally, CD8αβCD44high cells from DKO mice are able to secrete IFN-γ in response to IL-12 and IL-18 in the absence of cognate Ag. When challenged with anti-CD3 in vivo, nearly half of these cells produce IFN-γ within 3 h. When purified CD8αβCD44high cells from Thy1.2.DKO mice were transferred into Thy1.1 DKO recipients and then challenged with Listeria monocytogenes, an Ag-specific anti-L. monocytogenes response was observed 6 days later. Our data suggest that non-class Ia-selected CD8αβCD44high cells in naive animals can respond rapidly to Ag and play a role in the innate as well as the early phase of the acquired immune response.

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Section: Thymus-dependent Memory Phenotype Cd8 T Cells Inmentioning

confidence: 99%

Thymus-Dependent Memory Phenotype CD8 T Cells in Naive B6.H-2Kb−/−Db−/− Animals Mediate an Antigen-Specific Response against Listeria monocytogenes

Berg

Murray

et al. 2005

The Journal of Immunology

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“…H2-M3 and K d H chain and ␤ 2 -microglobulin were expressed as recombinant proteins in Escherichia coli, purified from inclusion bodies, and refolded in the presence of ϳ60 g/ml LLO 91-99 peptide (for H2-K d ) or fMIGWII(A) peptide (for H2-M3). H2-M3 tetramers generated with both the hexamer (fMIGWII) and the heptamer (fMIGWIIA) forms of the listerial LemA epitope specifically stain cells from Listeria-infected mice (25); in the experiments shown in this study, tetramers made with the two peptides were used interchangeably. Peptides were synthesized by Research Genetics (Huntsville, AL).…”

Section: Generation Of Tetramersmentioning

confidence: 99%

H2-M3-Restricted Memory T Cells: Persistence and Activation Without Expansion

Kerksiek

Ploß

Leiner

et al. 2003

The Journal of Immunology

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H2-M3-restricted T cells respond more rapidly to primary Listeria monocytogenes infection than conventional MHC class Ia-restricted T cells. Reinfection with L. monocytogenes, while inducing explosive proliferation of H2-Kd-restricted T cells, does not stimulate significant expansion of H2-M3-restricted CTL. These disparate responses to reinfection are apparent within 5 days of primary L. monocytogenes infection. However, H2-M3-restricted memory T cells are generated, and are indistinguishable from classically restricted T cells in terms of cell surface memory markers and longevity. Early responses of H2-M3- and H2-Kd-restricted memory T cells to reinfection are similar, with increases in size and expression of activation markers. Interestingly, priming of H2-M3-restricted T cells with an L. monocytogenes-derived N-formyl peptide plus anti-CD40 generates memory T cells that expand upon re-exposure to Ag during L. monocytogenes infection. Our data indicate that disparate H2-M3- and MHC class Ia-restricted memory T cell responses reflect intrinsic differences between these T cell populations. Although distinct proliferative programs appear to be hardwired in these populations during primary L. monocytogenes infection, under different inflammatory circumstances M3-restricted T cell populations can maintain the ability to expand upon re-exposure to Ag.

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“…The magnitude of Listeria-specific M3-restricted T-cell responses seems to vary considerably from mouse to mouse even with genetically identical mice, but fMIGWII is always the immunodominant epitope presented by M3 molecules during Listeria infection (6,20). Adoptive transfer of an fMIGWII-specific T-cell clone into naïve mice resulted in some degree of protection against subsequent challenge with L. monocytogenes (18).…”

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confidence: 99%

TheListeria monocytogenes lemAGene Product Is Not Required forIntracellular Infection or To Activate fMIGWII-Specific TCells

et al. 2003

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Clearance of the intracellular bacterial pathogen Listeria monocytogenes requires antigen-specific CD8؉ T cells. Recently it was shown that activation of class Ib major histocompatibility complex (MHC)-restricted CD8 ؉ T cells alone is sufficient for immune protection against listeriae. A major component of the class Ib MHC-restricted T-cell response is T cells that recognize formylated peptide antigens presented by M3 molecules. Although three N-formylated peptides derived from L. monocytogenes are known to bind to M3 molecules, fMIGWII is the immunodominant epitope presented by M3 during infection of mice. The source of fMIGWII peptide is the L. monocytogenes lemA gene, which encodes a 30-kDa protein of unknown function. In this report, we describe the generation of two L. monocytogenes lemA deletion mutants. We show that lemA is not required for growth of listeriae in tissue culture cells or for virulence during infection of mice. Surprisingly, we found that fMIGWII-specific T cells were still primed following infection with lemA mutant listeriae, suggesting that L. monocytogenes contains at least one additional antigen that is cross-reactive with the fMIGWII epitope. This cross-reactive antigen appears to be a small protease-resistant molecule that is secreted by L. monocytogenes.

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

Cited by 17 publications

References 35 publications

Thymus-Dependent Memory Phenotype CD8 T Cells in Naive B6.H-2Kb−/−Db−/− Animals Mediate an Antigen-Specific Response against Listeria monocytogenes

Thymus-Dependent Memory Phenotype CD8 T Cells in Naive B6.H-2Kb−/−Db−/− Animals Mediate an Antigen-Specific Response against Listeria monocytogenes

H2-M3-Restricted Memory T Cells: Persistence and Activation Without Expansion

TheListeria monocytogenes lemAGene Product Is Not Required forIntracellular Infection or To Activate fMIGWII-Specific TCells

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