Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients

Gonzalez, FE; Ramirez M.; Allerbring, EB; Fasching, N; Lundqvist, A; Poschke, I; Achour, A; Saazar-Onfray, F

Abstract

Background: Melanocortin 1 Receptor (MC1R) is expressed in a majority of melanoma biopsies and cell lines. We previously demonstrated that three hydrophobic low-affinity HLA-A2-restricted MC1R-derived peptides: MC1R(291-298), MC1 R244-252 and Mc1 R283-291 can elicit cytotoxic T-lymphocytes (CTL) responses from normal donor peripheral blood lymphocytes (PBL). Moreover, peptide-specific CTL recognized a panel of MHC-matched melanomas, demonstrating that human melanoma cell lines naturally present MC1R epitopes. However, the natural presence of MC1R-specific T cells in melanoma patient's tumour and blood remains unknown. Methods: The presence of anti-MC1R specific CD8(+) T cells was established in a population of melanoma-specific T cells derived from peripheral blood mononuclear cells (PBMC) and tumour-infiltrating lymphocytes (TIL) from HLA-A2(+) melanoma patients. Results: CTLs specific for the three MC1R-derived peptides that lysed allogeneic HLA-A2(+)MC1R(+) melanomas were elicited from PBMC, demonstrating the existence of an anti-MC1R T cell repertoire in melanoma patients. Moreover, TILs also recognized MC1R epitopes and HLA-A2(+) melanoma cell lines. Finally, HLA-A2/MC1R(244)-specific CD8(+) T cell clones derived from TILs and a subset of MCI R-291 specific TILs were identified using HLA-A2/MC1R tetramers. Conclusion: Our results demonstrate that MC1R-derived peptides are common immunogenic epitopes for melanoma-specific CTLs and TILs, and may thus be useful for the development of anti-melanoma immunotherapy. (C) 2013 Elsevier GmbH. All rights reserved.

Más información

Título según WOS: Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients
Título de la Revista: IMMUNOBIOLOGY
Volumen: 219
Número: 3
Editorial: ELSEVIER GMBH, URBAN & FISCHER VERLAG
Fecha de publicación: 2014
Página de inicio: 189
Página final: 197
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0171298513001770
DOI:

10.1016/j.imbio.2013.10.002

Notas: ISI