Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells

Flavio Salazar-Onfray, Tsutomu Nakazawa, Vijay Chhajlani, Max Petersson, Klas Kärre, Giuseppe Masucci, Esteban Celis, Alessandro Sette, Scott Southwood, Ettore Appella, Rolf Kiessling

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Human melanoma-specific HLA-A2 restricted CTLs have recently been shown to recognize antigens expressed by melanoma lines and normal melanocytes, including Melan-A/Mart-1, gp100, gp75, and tyrosinase. Herein, we define HLA- A2-restricted CTL epitopes from a recently cloned melanocortin 1 receptor (MC1R), which belongs to a new subfamily of the G-protein-coupled receptors expressed on melanomas and melanocytes. Thirty-one MC1R-derived peptides were selected on the basis of HLA-A2-specific motifs and tested for their HLA-A2 binding capacity. Of a group of 12 high or intermediate HLA-A2 binding peptides, three nonamers, MC1R244 (TILLGIFFL), MC1R283 (FLALIICNA), and MC1R291 (AIIDPLIYA), were found to induce peptide-specific CTLs from peripheral blood mononuclear cells of healthy HLA-A2+ donors after repeated in vitro stimulation with peptide-pulsed antigen-presenting cells. The CTLs raised against these three HLA-A2+-restricted peptides could recognize naturally processed peptides from HLA-A2+ melanomas and from Cos7 cells cotransfected with MC1R and HLA-A2. CTLs induced by the MC1R291 peptide (but not induced or induced only to a very low extent by the other two MCR1 peptide epitopes) showed cross-reactions with two other members of the melanocortin receptor family, which are more broadly expressed on other tissues. Taken together, our findings have implications in relation both to autoimmunity and immunotherapy of malignant melanomas.

Original languageEnglish (US)
Pages (from-to)4348-4355
Number of pages8
JournalCancer Research
Volume57
Issue number19
StatePublished - Oct 1 1997
Externally publishedYes

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Receptor, Melanocortin, Type 1
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
Melanoma
Peptides
Melanocytes
Epitopes
Melanocortin Receptors
MART-1 Antigen
Melanoma-Specific Antigens
MSH receptor
Monophenol Monooxygenase
Cross Reactions
Antigen-Presenting Cells
G-Protein-Coupled Receptors
Autoimmunity
Immunotherapy
Blood Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells. / Salazar-Onfray, Flavio; Nakazawa, Tsutomu; Chhajlani, Vijay; Petersson, Max; Kärre, Klas; Masucci, Giuseppe; Celis, Esteban; Sette, Alessandro; Southwood, Scott; Appella, Ettore; Kiessling, Rolf.

In: Cancer Research, Vol. 57, No. 19, 01.10.1997, p. 4348-4355.

Research output: Contribution to journalArticle

Salazar-Onfray, F, Nakazawa, T, Chhajlani, V, Petersson, M, Kärre, K, Masucci, G, Celis, E, Sette, A, Southwood, S, Appella, E & Kiessling, R 1997, 'Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells', Cancer Research, vol. 57, no. 19, pp. 4348-4355.
Salazar-Onfray, Flavio ; Nakazawa, Tsutomu ; Chhajlani, Vijay ; Petersson, Max ; Kärre, Klas ; Masucci, Giuseppe ; Celis, Esteban ; Sette, Alessandro ; Southwood, Scott ; Appella, Ettore ; Kiessling, Rolf. / Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells. In: Cancer Research. 1997 ; Vol. 57, No. 19. pp. 4348-4355.
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abstract = "Human melanoma-specific HLA-A2 restricted CTLs have recently been shown to recognize antigens expressed by melanoma lines and normal melanocytes, including Melan-A/Mart-1, gp100, gp75, and tyrosinase. Herein, we define HLA- A2-restricted CTL epitopes from a recently cloned melanocortin 1 receptor (MC1R), which belongs to a new subfamily of the G-protein-coupled receptors expressed on melanomas and melanocytes. Thirty-one MC1R-derived peptides were selected on the basis of HLA-A2-specific motifs and tested for their HLA-A2 binding capacity. Of a group of 12 high or intermediate HLA-A2 binding peptides, three nonamers, MC1R244 (TILLGIFFL), MC1R283 (FLALIICNA), and MC1R291 (AIIDPLIYA), were found to induce peptide-specific CTLs from peripheral blood mononuclear cells of healthy HLA-A2+ donors after repeated in vitro stimulation with peptide-pulsed antigen-presenting cells. The CTLs raised against these three HLA-A2+-restricted peptides could recognize naturally processed peptides from HLA-A2+ melanomas and from Cos7 cells cotransfected with MC1R and HLA-A2. CTLs induced by the MC1R291 peptide (but not induced or induced only to a very low extent by the other two MCR1 peptide epitopes) showed cross-reactions with two other members of the melanocortin receptor family, which are more broadly expressed on other tissues. Taken together, our findings have implications in relation both to autoimmunity and immunotherapy of malignant melanomas.",
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AU - Salazar-Onfray, Flavio

AU - Nakazawa, Tsutomu

AU - Chhajlani, Vijay

AU - Petersson, Max

AU - Kärre, Klas

AU - Masucci, Giuseppe

AU - Celis, Esteban

AU - Sette, Alessandro

AU - Southwood, Scott

AU - Appella, Ettore

AU - Kiessling, Rolf

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