The Specificity of Effector T Cells Activated by Tumours Induced by Murine Oncornaviruses

Shellam, Geoffrey; Knight, Richard; Mitchison, N. A.; Gorczynski, Reginald M.; Maoz, Arieh

doi:10.1111/j.1600-065x.1976.tb00204.x

Cited by 9 publications

(6 citation statements)

References 72 publications

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“…Furthermore, the demonstration that immunological memory for a cytotoxic T-cell response can be generated by in vivo immunization with an inactivated virus ( Fig. 1), is in accord with the observation of Shellam et al on oncornaviruses (27), and may be relevant to the design of vaccination procedures against these kinds of viruses. In this discussion, however, we shall concentrate on the effector phase of the response and particularly on the implications of the lysis of target cells coated with inactivated Sendai virus.…”

Section: Discussionsupporting

confidence: 85%

Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.

Schrader

Edelman

1977

The Journal of Experimental Medicine

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Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.

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Section: Discussionsupporting

confidence: 85%

Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.

Schrader

Edelman

1977

The Journal of Experimental Medicine

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“…Support for this concept comes also from the fact that among the influenza-specified pelypeptides only H, N, and matrix protein can be detected in plasma membrane preparations of infected cells (27). Furthermore, recent results in the oncornavirus system suggest that cytotoxic T cells specifically recognize the internal virion antigen p3o on the surface of virus-transformed target cells (28). Direct evidence for the role of matrix protein in cross-reactive killing by cytotoxic T cells may come from blocking experiments with anti-matrix antibody.…”

Section: Immunization Of Mice With Type a Influenza Virus Results In mentioning

confidence: 99%

Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells

Braciale¹

1977

The Journal of Experimental Medicine

109

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Two distinct subpopulations of cytotoxic T cells are generated in the primary or secondary response of mice to type A influenza viruses. One subpopulation is specific for the immunizing virus strain. The other subpopulation shows a high degree of cross-reactivity for heterologous type A virus of a different subtype. This report examines the possibility that distinct influenza virus antigens, expressed on the surface of the infected cell, are recognized by the different subpopulations of influenza-specific cytotoxic T cells. Data are presented which demonstrate that influenza A matrix protein, an internal virion antigen, is detectable on the surface of target cells infected with influenza A viruses of different subtypes. Since this viral antigen is type specific, i.e., serologically cross-reactive among all type A influenza viruses, it could serve as the target for cross-reactive cytotoxic T cells. To further examine the specificity of the two cytotoxic T-cell subpopulations, experiments were carried out by using the inhibitor of glycoprotein synthesis - 2-Deoxy-D-Glucose 2-DG. These experiments examine first the effect of 2-DG on the expression of influenza matrix protein and viral glycoprotein on the infected cell surface and second, the susceptibility of 2-DG-treated target cells to lysis by cytotoxic T cells. 2-DG inhibits the expression of the viral hemagglutinin glycoprotein on the cell surface but does not inhibit the expression of the nonglycosylated matrix protein. Furthermore, inhibition of glycoprotein synthesis in infected target cells abrogates the reactivity of infected target cells to lysis by virus strain-specific but not cross- reactive cytotoxic T cells. These findings suggest that the influenza glycoproteins (hemagglutinin and/or neuraminidase) and the nonglycosylated matrix protein are the targets for the virus strain- specific and cross-reactive cytotoxic T cells, respectively. These results are discussed in the light of available information on influenza virus structure and the biology of influenza infection and in terms of current models for cytotoxic T-cell recognition of virus-infected cells.

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“…In one series of reports, increased cytolytic activity was found after short-term culture (3-24 h) of lymphocytes from tumour-bearer or tumour-immune animals (de Landazuri & Herberman, 1972;Laux & Lausch, 1974;Vasudevan et al, 1974;Gorczynski & Tigelaar, 1975;Shellam et al, 1976), such in vitro activated cells being apparently capable of causing specific tumour rejection in vivo (Blasecki & Trevethia, 1975). In the mouse studies, the cytotoxic cells were shown to be sensitive to anti-6 serum (Vasudevan et al, l1974;Gorezinski & Tigelaar, 1975) and were therefore not NK cells (Herberman & Holden, 1978).…”

Section: Resultsmentioning

confidence: 99%

Spontaneous development of cytotoxic activity in cultured lymphnode cells from tumour-bearing rats

Robins¹,

Rees²,

Brooks³

et al. 1979

Br J Cancer

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The Specificity of Effector T Cells Activated by Tumours Induced by Murine Oncornaviruses

Cited by 9 publications

References 72 publications

Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.

Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.

Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells

Spontaneous development of cytotoxic activity in cultured lymphnode cells from tumour-bearing rats

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