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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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Proliferation of  RAG-1−/− F5 T cells to NP  peptides from all three strains of  influenza viruses. RAG-1−/−  spleen cells (104/well) were stimulated by varying concentrations  of the viral peptides and 2 × 105  mitomycin C–treated syngeneic  spleen cells per well as accessory  cells. The dotted line depicts T  cell proliferation when no peptide is added.
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Figure 3: Proliferation of RAG-1−/− F5 T cells to NP peptides from all three strains of influenza viruses. RAG-1−/− spleen cells (104/well) were stimulated by varying concentrations of the viral peptides and 2 × 105 mitomycin C–treated syngeneic spleen cells per well as accessory cells. The dotted line depicts T cell proliferation when no peptide is added.

Mentions: Since most of the experiments were carried out in transgenic mice which may undergo endogenous V-D-J/V-J rearrangement, it is possible to explain the distinct specificity at the inductive and the effector phase by postulating the existence of two populations of T cells: one expresses the transgenic receptors that have the specificity of the original F5 clones, whereas the other gains the specificity for the H1N1 peptide as a result of pairing a transgenic TCR chain with an endogenous chain. We used spleen cells from the Rag-1−/− F5 mice as the responder T cells to rule out this possibility. Again, the H1N1 NP peptide induces significant proliferation of the Rag-1–deficient F5 T cells (Fig. 3). This result confirmed that the F5 TCR has reactivity to the H1N1 NP peptide.


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)

Proliferation of  RAG-1−/− F5 T cells to NP  peptides from all three strains of  influenza viruses. RAG-1−/−  spleen cells (104/well) were stimulated by varying concentrations  of the viral peptides and 2 × 105  mitomycin C–treated syngeneic  spleen cells per well as accessory  cells. The dotted line depicts T  cell proliferation when no peptide is added.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Proliferation of RAG-1−/− F5 T cells to NP peptides from all three strains of influenza viruses. RAG-1−/− spleen cells (104/well) were stimulated by varying concentrations of the viral peptides and 2 × 105 mitomycin C–treated syngeneic spleen cells per well as accessory cells. The dotted line depicts T cell proliferation when no peptide is added.
Mentions: Since most of the experiments were carried out in transgenic mice which may undergo endogenous V-D-J/V-J rearrangement, it is possible to explain the distinct specificity at the inductive and the effector phase by postulating the existence of two populations of T cells: one expresses the transgenic receptors that have the specificity of the original F5 clones, whereas the other gains the specificity for the H1N1 peptide as a result of pairing a transgenic TCR chain with an endogenous chain. We used spleen cells from the Rag-1−/− F5 mice as the responder T cells to rule out this possibility. Again, the H1N1 NP peptide induces significant proliferation of the Rag-1–deficient F5 T cells (Fig. 3). This result confirmed that the F5 TCR has reactivity to the H1N1 NP peptide.

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