Hemagglutinin-specific complement-dependent antibody response to influenza infection

The host defense response to influenza infection is complex. Specific humoral antibodies develop to the strain-specific surface antigens, the hemagglutinin and the neuraminidase, and to the internal antigens (matrix and nucleoprotein) which are common to all influenza A viruses (1). Antibodies to the hemagglutinin, which is the major surface antigen, neutralize viral infectivity (2). In addition to antibodies which have been detected against virion antigens, a cytotoxic T-cell response with specificity against the viral hemagglutinin on influenza-infected target cells (3-5) has been recently described. A more cross-reactive cytotoxic T-cell response has also been observed when a nonpermissively infected target cell is used in cytotoxicity assays (6,7). The present report describes the development during influenza infection and after vaccination of a cytolytic humoral antibody response which is directed against the hemagglutinin on infected target cells. This antibody-mediated lysis of infected cells in complement dependent, as has been reported with other virus infections (8-11).

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Hemagglutinin-specific cytotoxic T-cell response during influenza infection.

Journal of Experimental Medicine ◽

10.1084/jem.146.3.893 ◽

1977 ◽

Vol 146 (3) ◽

pp. 893-898 ◽

Cited By ~ 30

Author(s):

F A Ennis ◽

W J Martin ◽

M W Verbonitz

Keyword(s):

T Cell ◽

Target Cell ◽

Cell Response ◽

Influenza A ◽

Influenza Infection ◽

T Cell Response ◽

Cytotoxic T Cell ◽

Target Cells ◽

Cervical Lymph Nodes ◽

Cytotoxic Response

Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.

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Modification of Cytotoxic T-Cell Response Patterns by Administration of Hemagglutinin-Specific Monoclonal Antibodies to Mice Infected with Influenza A Viruses

Hybridoma ◽

10.1089/hyb.1.1982.1.149 ◽

1982 ◽

Vol 1 (2) ◽

pp. 149-159 ◽

Cited By ~ 2

Author(s):

NEIL GREENSPAN ◽

PETER C. DOHERTY

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

Cell Response ◽

Influenza A ◽

T Cell Response ◽

Cytotoxic T Cell ◽

Response Patterns ◽

Influenza A Viruses

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Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype.

Journal of Experimental Medicine ◽

10.1084/jem.148.2.534 ◽

1978 ◽

Vol 148 (2) ◽

pp. 534-543 ◽

Cited By ~ 108

Author(s):

P C Doherty ◽

W E Biddison ◽

J R Bennink ◽

B B Knowles

Keyword(s):

T Cells ◽

T Cell ◽

Vaccinia Virus ◽

Influenza A ◽

Present Report ◽

Primary Response ◽

Cytotoxic T Cell ◽

Target Cells ◽

Influenza A Viruses ◽

Cytotoxic T Cell Responses

Secondary effector T-cell populations generated by cross-priming with heterologous influenza A viruses operate only in H-2K or H-2D compatible situations, when assayed on SV40-transformed target cells infected with a range of influenza A viruses. The H2-Kb allele is associated with a total failure in the generation of influenza-immune cytotoxic T cells, though this is not seen for the primary response to vaccinia virus. In both influenza and vaccinia development of effector T cells operating at H-2Db is greatly depressed in B10.A(2R) (kkkddb) and B10.A(4R) (kkbbbb), but not in B10 (bbbbbb), mice. However, there is no defect in viral antigen expression at either H-2Kk or H-2Db in B10.A(2R) target cells. This apparently reflects some inadequacy in the stimulator environment, as (A/J X B6) F1 T cells can be induced to respond at H-2Db when exposed to vaccinia virus in an irradiated B6 but not in a B10.A(4R) recipient. The present report, together with the accompanying paper by Zinkernagel and colleagues, records the first rigorous demonstration of both a nonresponder situation and a probable Ir-gene effect for conventional infectious viruses. Possible implications for the evolution of H-2 polymorphism and mechanisms of Ir gene function are discussed.

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Rectification of Age-Associated Deficiency in Cytotoxic T Cell Response to Influenza A Virus by Immunization with Immune Complexes

The Journal of Immunology ◽

10.4049/jimmunol.179.9.6153 ◽

2007 ◽

Vol 179 (9) ◽

pp. 6153-6159 ◽

Cited By ~ 31

Author(s):

Biao Zheng ◽

Yongxin Zhang ◽

Hongxia He ◽

Ekaterina Marinova ◽

Kirsten Switzer ◽

...

Keyword(s):

T Cell ◽

Influenza A Virus ◽

Immune Complexes ◽

Cell Response ◽

Influenza A ◽

T Cell Response ◽

Cytotoxic T Cell

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Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.

Journal of Experimental Medicine ◽

10.1084/jem.145.3.557 ◽

1977 ◽

Vol 145 (3) ◽

pp. 557-568 ◽

Cited By ~ 179

Author(s):

R B Effros ◽

P C Doherty ◽

W Gerhard ◽

J Bennink

Keyword(s):

T Cell ◽

Influenza A ◽

Competitive Inhibition ◽

Influenza Viruses ◽

Cytotoxic T Cell ◽

Considerable Proportion ◽

Target Cells ◽

Cell Mediated Immunity ◽

Influenza A Viruses ◽

Apparent Lack

Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.

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Cytotoxic T cell response to minor histocompatibility antigens: apparent lack of H-2 restriction in killers stimulated by membrane fragments.

Journal of Experimental Medicine ◽

10.1084/jem.156.1.217 ◽

1982 ◽

Vol 156 (1) ◽

pp. 217-229 ◽

Cited By ~ 2

Author(s):

L M Pilarski ◽

D Vergidis

Keyword(s):

T Cell ◽

Cell Response ◽

T Cell Response ◽

Cytotoxic T Cell ◽

Adherent Cell ◽

Target Cells ◽

Histocompatibility Antigens ◽

Intact Cells ◽

Apparent Lack ◽

Minor Histocompatibility Antigens

The secondary cytotoxic T cell response of BALB/c to B10.D2 or DBA/2 minor histocompatibility antigens in vitro requires the participation of an adherent cell. Nylon wool-passed spleen cells were only able to respond to nonadherent intact stimulator cells, or to membrane fragments derived from those cells, if a syngeneic adherent cell were present in the cultures. When the H-2 restriction properties of cytotoxic cells generated in response to various types of stimulation were analyzed, it was found that responses to B10.D2 or DBA/2 intact cells were always H-2 restricted. Responses to syngeneic adherent cells presenting B10.D2 or DBA.2 freeze-thaw antigen were either entirely or predominantly lacking in H-2 restriction as defined by efficient competition by B10 (H-2b) cold target cells. These unrestricted killers appeared to recognize minor histocompatibility as an independent determinant rather than as an H-2d/minors moiety cross-reaction with H-2b, because they were not absorbed by BALB.B (H-2b) macrophage monolayers, but were absorbed by B10 monolayers. Similarly, B10 but not BALB.B cold targets were able to compete for the anti-B10.D2 killers. These experiments eliminate the possibility that the lack of restriction was due to an H-2b restricted receptor cross-reactive with H-2b. Possible models to explain these findings are discussed.

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