Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes

Implications for peptide-based immunotherapy

Licia Rivoltini, Douglas J. Loftus, Kathleen Barracchini, Flavio Arienti, Arabella Mazzocchi, William E. Biddison, Michael L. Salgaller, Ettore Appella, Giorgio Parmiani, Francesco M. Marincola

Research output: Contribution to journalArticle

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Abstract

Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (∼20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-127-35, G9154, and G9280 Flu M158-66) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.

Original languageEnglish
Pages (from-to)3882-3891
Number of pages10
JournalJournal of Immunology
Volume156
Issue number10
Publication statusPublished - May 15 1996

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Melanoma-Specific Antigens
HLA-A2 Antigen
Immunotherapy
Melanoma
Glycoproteins
Peptides
HLA-A Antigens
MART-1 Antigen
Cellular Immunity
Population
Inhibitory Concentration 50
Epitopes
Tissue Donors
HLA-A*02:01 antigen

ASJC Scopus subject areas

  • Immunology

Cite this

Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes : Implications for peptide-based immunotherapy. / Rivoltini, Licia; Loftus, Douglas J.; Barracchini, Kathleen; Arienti, Flavio; Mazzocchi, Arabella; Biddison, William E.; Salgaller, Michael L.; Appella, Ettore; Parmiani, Giorgio; Marincola, Francesco M.

In: Journal of Immunology, Vol. 156, No. 10, 15.05.1996, p. 3882-3891.

Research output: Contribution to journalArticle

Rivoltini, Licia ; Loftus, Douglas J. ; Barracchini, Kathleen ; Arienti, Flavio ; Mazzocchi, Arabella ; Biddison, William E. ; Salgaller, Michael L. ; Appella, Ettore ; Parmiani, Giorgio ; Marincola, Francesco M. / Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes : Implications for peptide-based immunotherapy. In: Journal of Immunology. 1996 ; Vol. 156, No. 10. pp. 3882-3891.
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abstract = "Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (∼20{\%}) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50{\%} inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-127-35, G9154, and G9280 Flu M158-66) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.",
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AB - Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (∼20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-127-35, G9154, and G9280 Flu M158-66) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.

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