CD8 T Cell Responses to Infectious Pathogens

Wong, Phillip; Pamer, Eric G.

doi:10.1146/annurev.immunol.21.120601.141114

Cited by 372 publications

(308 citation statements)

References 335 publications

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“…In order to clear the invading virus, the virus-specific CD8 T cells must migrate to sites of infection (56), which is mediated by the interaction of chemokine receptors and chemokines. It is known that CCR5 expressed on memory CTLs is needed for their recruitment to the airways during the early stages of the recall response (30).…”

Section: Cross-response Of Bulk Ctls Against Pdmh1n1 In Healthy Indivmentioning

confidence: 99%

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

138

127

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While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣). Using influenza A virus matrix protein 1 (M1 58-66 ) epitope-specific CTLs isolated from healthy HLA-A2 ؉ individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66 -specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 ؉ individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

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Section: Cross-response Of Bulk Ctls Against Pdmh1n1 In Healthy Indivmentioning

confidence: 99%

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

138

127

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“…Thus, CyaA appears to be a safe and potent vehicle for in vivo Ag delivery to CD11b high DC (21), leading to CD8 ϩ T cell priming. However, the generation of optimal CD8 ϩ T cell responses for prophylactic and therapeutic purposes may require the simultaneous activation of CD4 ϩ T cell responses (22)(23)(24)(25)(26)(27). Therefore, successful vaccinal strategies will need the simultaneous delivery of both CD4 ϩ and CD8 ϩ T cell epitopes to APC for efficient T cell priming.…”

Section: Antigen Targeting To Cd11b Allows Efficient Presentation Of Cd4mentioning

confidence: 99%

Antigen Targeting to CD11b Allows Efficient Presentation of CD4+ and CD8+ T Cell Epitopes and In Vivo Th1-Polarized T Cell Priming

Schlecht

Loucká

Najar

et al. 2004

The Journal of Immunology

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Bordetella pertussis adenylate cyclase (CyaA) is an invasive bacterial toxin that delivers its N-terminal catalytic domain into the cytosol of eukaryotic cells bearing the αMβ2 integrin (CD11b/CD18), such as myeloid dendritic cells. This allows use of engineered CyaA for targeted delivery of CD8+ T cell epitopes into the MHC class I pathway of APC and induction of robust and protective cytotoxic responses. In this study, we demonstrate that CyaA can efficiently codeliver both a CD8+ T cell epitope (OVA257–264) and a CD4+ T cell epitope (MalE100–114) into, respectively, the conventional cytosolic or endocytic routes of processing of murine bone marrow-derived dendritic cells. Upon CyaA delivery, a strong potentiation of the MalE100–114 CD4+ T cell epitope presentation is observed as compared with the MalE protein, which depends on CyaA interaction with its CD11b receptor and its subsequent clathrin-mediated endocytosis. In vivo, CyaA induces strong and specific Th1 CD4+ and CD8+ T cell responses against, respectively, the MalE100–114 and OVA257–264 epitopes. These results underscore the potency of CyaA for design of new vaccines.

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“…3 Wild-type L. monocytogenes strain 10403s was originally provided by D. Portnoy (University of California, Berkeley, CA). To generate the fMIG neg L. monocytogenes strain, the LemA region of L. monocytogenes was mutated in the fMIGWII epitope to fMIVIL by the PCR overlap extension method.…”

Section: Bacterial Strainsmentioning

confidence: 99%

“…CD8 ϩ T cells recognize pathogen-derived peptides presented on MHC class I molecules and are important for clearance of many invading pathogens (3). MHC class I molecules can be divided into two groups.…”

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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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CD8 T Cell Responses to Infectious Pathogens

Cited by 372 publications

References 335 publications

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Antigen Targeting to CD11b Allows Efficient Presentation of CD4+ and CD8+ T Cell Epitopes and In Vivo Th1-Polarized T Cell Priming

Promiscuity of MHC Class Ib-Restricted T Cell Responses

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