Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells

Townsend, Alain; McMichael, Andrew J.; Carter, N.P.; Huddleston, Joyce A.; Brownlee, George G.

doi:10.1016/0092-8674(84)90187-9

Cited by 309 publications

(172 citation statements)

References 41 publications

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“…A long literature has characterized the CD8 ϩ CTL response to conserved internal Ags, predominantly NP (23)(24)(25)(26), and the response of CD4 ϩ T cells as measured by proliferation, help for Ab and CTL responses, and cytokine production (27)(28)(29). Th cells specific for NP or M can help for subsequent Ab responses to HA (27), suggesting a mechanism for accelerated responses to a mismatched virus strain at the time of challenge.…”

mentioning

confidence: 99%

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Benton

Misplon

et al. 2001

The Journal of Immunology

126

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The mechanisms of broad cross-protection to influenza viruses of different subtypes, termed heterosubtypic immunity, remain incompletely understood. We used knockout mouse strains to examine the potential for heterosubtypic immunity in mice lacking IgA, all Ig and B cells, NKT cells (CD1 knockout mice), or γδ T cells. Mice were immunized with live influenza A virus and compared with controls immunized with unrelated influenza B virus. IgA−/− mice survived full respiratory tract challenge with heterosubtypic virus that was lethal to controls. IgA−/− mice also cleared virus from the nasopharynx and lungs following heterosubtypic challenge limited to the upper respiratory tract, where IgA has been shown to play an important role. Ig−/− mice controlled the replication of heterosubtypic challenge virus in the lungs. Acute depletion of CD4+ or CD8+ T cell subsets abrogated this clearance of virus, thus indicating that both CD4+ and CD8+ T cells are required for protection in the absence of Ig. These results in Ig−/− mice indicate that CD4+ T cells can function by mechanisms other than providing help to B cells for the generation of Abs. Like wild-type mice, CD1−/− mice and γδ−/− mice survived lethal heterosubtypic challenge. Acute depletion of CD4+ and CD8+ cells abrogated heterosubtypic protection in γδ−/− mice, but not B6 controls, suggesting a contribution of γδ T cells. Our results demonstrate that the Ab and cellular subsets deficient in these knockout mice are not required for heterosubtypic protection, but each may play a role in a multifaceted response that as a whole is more effective than any of its parts.

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confidence: 99%

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Benton

Misplon

et al. 2001

The Journal of Immunology

126

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“…protective cross‐reactivity to lethal infection with influenza A virus of a serotype different from the virus initially encountered. It was expected that protection would be afforded by cytotoxic lymphocytes, known to respond preferentially (in an ‘immunodominant way’) to cross‐reactive antigens such as NP 3 . Contrary to expectation however, it was found that mice deficient in CD8 molecules performed HSI normally, whereas B cell‐deficient animals did not 4 .…”

Section: Protection Afforded By Influenza Antigens Other Than Haemaggmentioning

confidence: 92%

Rationale for treating human influenza infections by passive transfer of specific antibodies

Virelizier

2007

Influenza Resp Viruses

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The fear of a potential pandemic with a highly pathogenic influenza A virus, such as the avian virus H5N1, has rightly prompted multidisciplinary reflections and calls for better preparedness all over the world. In terms of therapeutic aspects, most of the focus has been on vaccines and antivirals. The present ‘opinion paper’ intends to discuss a different therapeutic approach, although not mutually exclusive to the two others quoted above. We here propose an approach, based on well‐documented experimental evidence in animal models, in which a short series of human monoclonal antibodies adapted to the probable pandemic strain, specific for external antigens of that influenza virus and shown in vitro and in experimental models to have neutralizing properties, are prepared and stockpiled for administration to people recently exposed to the pandemic virus.

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Section: Discussionmentioning

confidence: 99%

“…Although the two envelope proteins of MV have been shown to be important in immunization (de Vries et al, 1988;Norrby & Gollmar, 1975;Drillien et al, 1988), the role of these and of other virus antigens in immunity is unknown. Studies with influenza A virus have now established that besides the envelope proteins, the nucleoprotein (NP) plays an important role, as it is implicated in the cytotoxic T lymphocyte response (Townsend et al, 1984).Studies with polyclonal antibodies suggested that MV was monotypic. However, comparison of laboratory-passaged viruses using monoclonal antibodies (MAbs) revealed the occurrence of epitope variations in the haemagglutinin and matrix proteins (Sheshberadaran et al, 1983).…”

mentioning

confidence: 99%

Expression of Measles Virus Nucleoprotein in Escherichia coli: Use of Deletion Mutants to Locate the Antigenic Sites

Buckland

Giraudon

Wild

1989

Journal of General Virology

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SUMMARYThree distinct antigenic determinants on the nucleoprotein (NP) of measles virus were localized. These epitopes were defined by three monoclonal antibodies, one of which recognized all measles virus field strains examined, whereas the other two were variable. A measles virus NP cDNA subclone representing 502 of the 525 amino acids was cloned into a bacterial expression vector plasmid (pRIT) and expressed as a Protein A-NP fusion protein in Escherichia coll. The expressed protein reacted with all three monoclonal antibodies. A series of NP gene deletions was constructed in order to locate the antigenic sites. The antigenic site identified on all measles virus strains studied, which was designated site I, was located between amino acids 122 and 150. The two variable epitopes were located at the C terminus of the protein (site II at 457 to 476; site III at 519 to 525). The structural and biological implications of these observations are discussed.Measles virus (MV) can cause both acute and persistent infections. Although the two envelope proteins of MV have been shown to be important in immunization (de Vries et al., 1988;Norrby & Gollmar, 1975;Drillien et al., 1988), the role of these and of other virus antigens in immunity is unknown. Studies with influenza A virus have now established that besides the envelope proteins, the nucleoprotein (NP) plays an important role, as it is implicated in the cytotoxic T lymphocyte response (Townsend et al., 1984).Studies with polyclonal antibodies suggested that MV was monotypic. However, comparison of laboratory-passaged viruses using monoclonal antibodies (MAbs) revealed the occurrence of epitope variations in the haemagglutinin and matrix proteins (Sheshberadaran et al., 1983). In our studies of field strains of MV isolated in Africa, we observed antigenic variation on the NP antigen only . Further, we were able to identify a common antigenic site on all virus strains examined, and two other epitopes which varied with the isolate.Studies with MAbs have been used in the elucidation of virus structure (Wiley et al., 1981) and in defining the heterogeneity of virus populations (Yewdell & Gerhard, 1981). Such studies result in better understanding of the correlation between the structure of proteins and their association with biological activity. Thus, MAbs to different epitopes on the haemagglutinin antigen distinguish regions that can be of use as targets for antibodies capable of passively protecting animals (Giraudon & Wild, 1985). Studies with neutralization-resistant mutants of a variety of viruses have shown single amino acid changes at the antigenic site (Wiley et al., 1981 ;Webster & Laver, 1980). However, this approach is limited by the nature of the biological activity, i.e. neutralization. The availability of cloned virus genes and the ability to express them in heterologous systems opens up further possibilities for the mapping of biological activities other than neutralization. Thus, the expression of subclones of the glycoprotein of Rift Valley fever virus...

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Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells

Cited by 309 publications

References 41 publications

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Rationale for treating human influenza infections by passive transfer of specific antibodies

Expression of Measles Virus Nucleoprotein in Escherichia coli: Use of Deletion Mutants to Locate the Antigenic Sites

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