title: Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients.
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: MC1R291-298, MC1R244-252 and MC1R283-291 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/MC1R244-specific CD8(+) T cell clones derived from TILs and a subset of MC1R291 specific TILs were identified using HLA-A2/MC1R tetramers.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Science for Life Laboratory, Centre for Infectious Medicine (CIM), Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden; Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, 8380492 Santiago, Chile.
authors.forename: Fermín E
authors.initials: FE
authors.lastname: González
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Marcos
authors.initials: M
authors.lastname: Ramírez
authors.affiliation: Science for Life Laboratory, Centre for Infectious Medicine (CIM), Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Eva B
authors.initials: EB
authors.lastname: Allerbring
authors.affiliation: Science for Life Laboratory, Centre for Infectious Medicine (CIM), Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Fasching
authors.affiliation: Department of Oncology and Pathology, Cancer Centre Karolinska (R8:01), Karolinska Institute, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lundqvist
authors.affiliation: Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Poschke
authors.affiliation: Science for Life Laboratory, Centre for Infectious Medicine (CIM), Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Adnane
authors.initials: A
authors.lastname: Achour
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. Electronic address: fsalazar@med.uchile.cl.
authors.forename: Flavio
authors.initials: F
authors.lastname: Salazar-Onfray
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000276:immunology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D044102:Receptor, Melanocortin, Type 1
keywords: Cytotoxic T lymphocytes; Immunotherapy; MC1R; Melanoma; Tumour infiltrating lymphocytes