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Costimulation by B7 modulates specificity of cytotoxic T lymphocytes: a missing link that explains some bystander T cell activation.

Zheng P, Liu Y - J. Exp. Med. (1997)

Bottom Line: However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL.Our results revealed that this is the case.These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center 10016, USA.

ABSTRACT
It has been proposed that some bystander T cell activation may in fact be due to T cell antigen receptor (TCR) cross-reactivity that is too low to be detected by the effector cytotoxic T lymphocyte (CTL). However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL. Here we report that transgenic T cells expressing a T cell receptor to influenza virus A/NT/68 nucleoprotein (NP) 366-374:Db complexes clonally expand and become effector CTLs in response to homologous peptides from either A/PR8/34 (H1N1), A/AA/60 (H2N2), or A/NT/68 (H3N2). However, the effector T cells induced by each of the three peptides kill target cells pulsed with NP peptides from the H3N2 and H2N2 viruses, but not from the H1N1 virus. Thus, NP366-374 from influenza virus H1N1 is the first TCR ligand that can induce T cell proliferation and differentiation without being recognized by CTLs. Since induction of T cell proliferation was mediated by antigen-presenting cells that express costimulatory molecules such as B7, we investigated if cytolysis of H1N1 NP peptide-pulsed targets can be restored by expressing B7-1 on the target cells. Our results revealed that this is the case. These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

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Induction of cytotoxicity of F5 T cells by viral peptides. Fine specificity of T cells induced by three different peptides. RAG-1+/+ F5 spleen  cells (5 × 105/ml) were stimulated with 0.1 μg/ml of H1N1 (a), H2N2 (b) or H3N2 (c) viral peptides for 4 d, and the viable cells were isolated and used  as effectors. Effector/target ratio is 60:1 for all groups. See Fig. 1 legend for details.
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Figure 4: Induction of cytotoxicity of F5 T cells by viral peptides. Fine specificity of T cells induced by three different peptides. RAG-1+/+ F5 spleen cells (5 × 105/ml) were stimulated with 0.1 μg/ml of H1N1 (a), H2N2 (b) or H3N2 (c) viral peptides for 4 d, and the viable cells were isolated and used as effectors. Effector/target ratio is 60:1 for all groups. See Fig. 1 legend for details.

Mentions: To test if all three related peptides are capable of inducing cytotoxicity from the transgenic T cells, we stimulated F5 spleen cells with NP peptides from all three strains of influenza viruses and tested the influenza-specific CTLs generated. In addition, we also compared the fine specificity of the CTL generated in each culture by using a target cell pulsed with three NP peptides and an unrelated control peptide. As shown in Fig. 4, a–c, all three influenza peptides induce mature CTLs capable of lysis H3N2 and H2N2 NP peptide–pulsed targets. These results demonstrated that the H1N1 NP peptide is capable of inducing the maturation of CTLs. Furthermore, although the H1N1 NP peptide-induced CTL is less potent than those induced by the H2N2 and H3N2 NP peptides, the relative lysis of the CTL towards three different peptides remains the same. These results substantiate the notion that T cells with the same fine specificity are stimulated by three different NP peptides.


Costimulation by B7 modulates specificity of cytotoxic T lymphocytes: a missing link that explains some bystander T cell activation.

Zheng P, Liu Y - J. Exp. Med. (1997)

Induction of cytotoxicity of F5 T cells by viral peptides. Fine specificity of T cells induced by three different peptides. RAG-1+/+ F5 spleen  cells (5 × 105/ml) were stimulated with 0.1 μg/ml of H1N1 (a), H2N2 (b) or H3N2 (c) viral peptides for 4 d, and the viable cells were isolated and used  as effectors. Effector/target ratio is 60:1 for all groups. See Fig. 1 legend for details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199130&req=5

Figure 4: Induction of cytotoxicity of F5 T cells by viral peptides. Fine specificity of T cells induced by three different peptides. RAG-1+/+ F5 spleen cells (5 × 105/ml) were stimulated with 0.1 μg/ml of H1N1 (a), H2N2 (b) or H3N2 (c) viral peptides for 4 d, and the viable cells were isolated and used as effectors. Effector/target ratio is 60:1 for all groups. See Fig. 1 legend for details.
Mentions: To test if all three related peptides are capable of inducing cytotoxicity from the transgenic T cells, we stimulated F5 spleen cells with NP peptides from all three strains of influenza viruses and tested the influenza-specific CTLs generated. In addition, we also compared the fine specificity of the CTL generated in each culture by using a target cell pulsed with three NP peptides and an unrelated control peptide. As shown in Fig. 4, a–c, all three influenza peptides induce mature CTLs capable of lysis H3N2 and H2N2 NP peptide–pulsed targets. These results demonstrated that the H1N1 NP peptide is capable of inducing the maturation of CTLs. Furthermore, although the H1N1 NP peptide-induced CTL is less potent than those induced by the H2N2 and H3N2 NP peptides, the relative lysis of the CTL towards three different peptides remains the same. These results substantiate the notion that T cells with the same fine specificity are stimulated by three different NP peptides.

Bottom Line: However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL.Our results revealed that this is the case.These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center 10016, USA.

ABSTRACT
It has been proposed that some bystander T cell activation may in fact be due to T cell antigen receptor (TCR) cross-reactivity that is too low to be detected by the effector cytotoxic T lymphocyte (CTL). However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL. Here we report that transgenic T cells expressing a T cell receptor to influenza virus A/NT/68 nucleoprotein (NP) 366-374:Db complexes clonally expand and become effector CTLs in response to homologous peptides from either A/PR8/34 (H1N1), A/AA/60 (H2N2), or A/NT/68 (H3N2). However, the effector T cells induced by each of the three peptides kill target cells pulsed with NP peptides from the H3N2 and H2N2 viruses, but not from the H1N1 virus. Thus, NP366-374 from influenza virus H1N1 is the first TCR ligand that can induce T cell proliferation and differentiation without being recognized by CTLs. Since induction of T cell proliferation was mediated by antigen-presenting cells that express costimulatory molecules such as B7, we investigated if cytolysis of H1N1 NP peptide-pulsed targets can be restored by expressing B7-1 on the target cells. Our results revealed that this is the case. These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

Show MeSH
Related in: MedlinePlus