Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35)

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Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35). / Loftus, D J; Squarcina, P; Nielsen, M B; Geisler, C; Castelli, C; Odum, N; Appella, E; Parmiani, G; Rivoltini, L.

In: Cancer Research, Vol. 58, No. 11, 1998, p. 2433-9.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Loftus, DJ, Squarcina, P, Nielsen, MB, Geisler, C, Castelli, C, Odum, N, Appella, E, Parmiani, G & Rivoltini, L 1998, 'Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35)', Cancer Research, vol. 58, no. 11, pp. 2433-9.

APA

Loftus, D. J., Squarcina, P., Nielsen, M. B., Geisler, C., Castelli, C., Odum, N., Appella, E., Parmiani, G., & Rivoltini, L. (1998). Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35). Cancer Research, 58(11), 2433-9.

Vancouver

Loftus DJ, Squarcina P, Nielsen MB, Geisler C, Castelli C, Odum N et al. Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35). Cancer Research. 1998;58(11):2433-9.

Author

Loftus, D J ; Squarcina, P ; Nielsen, M B ; Geisler, C ; Castelli, C ; Odum, N ; Appella, E ; Parmiani, G ; Rivoltini, L. / Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35). In: Cancer Research. 1998 ; Vol. 58, No. 11. pp. 2433-9.

Bibtex

@article{64dc30a0b0a411ddb538000ea68e967b,
title = "Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35)",
abstract = "The self-peptide MART1(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8+ T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1+ melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor-alpha and IFN-gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response.",
author = "Loftus, {D J} and P Squarcina and Nielsen, {M B} and C Geisler and C Castelli and N Odum and E Appella and G Parmiani and L Rivoltini",
note = "Keywords: Antigens, Neoplasm; Autoantigens; Clone Cells; Cytotoxicity, Immunologic; Databases, Factual; Epitope Mapping; Epitopes; HLA-A2 Antigen; Humans; Interleukin-2; Melanocytes; Melanoma; Neoplasm Proteins; Peptide Library; Phosphorylation; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; ZAP-70 Protein-Tyrosine Kinase",
year = "1998",
language = "English",
volume = "58",
pages = "2433--9",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "11",

}

RIS

TY - JOUR

T1 - Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35)

AU - Loftus, D J

AU - Squarcina, P

AU - Nielsen, M B

AU - Geisler, C

AU - Castelli, C

AU - Odum, N

AU - Appella, E

AU - Parmiani, G

AU - Rivoltini, L

N1 - Keywords: Antigens, Neoplasm; Autoantigens; Clone Cells; Cytotoxicity, Immunologic; Databases, Factual; Epitope Mapping; Epitopes; HLA-A2 Antigen; Humans; Interleukin-2; Melanocytes; Melanoma; Neoplasm Proteins; Peptide Library; Phosphorylation; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; ZAP-70 Protein-Tyrosine Kinase

PY - 1998

Y1 - 1998

N2 - The self-peptide MART1(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8+ T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1+ melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor-alpha and IFN-gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response.

AB - The self-peptide MART1(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8+ T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1+ melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor-alpha and IFN-gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response.

M3 - Journal article

C2 - 9622085

VL - 58

SP - 2433

EP - 2439

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -

ID: 8545522