Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients
González Bergas, Fermín
Ramírez Fernández, Marcos
Allerbring, Eva B.
Salazar Onfray, Flavio
Cita de ítem
Immunobiology 219 (2014) 189–197
Artículo de publicación ISI
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 melanomaspecific
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.
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
This work was supported
by grants from the Chilean National Fund for Scientific and Technological
Development (FONDECYT 1090238; F.S.-O.), the Fund
for the Promotion of Scientific and Technological Development
(FONDEF D11I1036; F.S.-O.), the Millennium Institute of Immunology
and Immunotherapy (P04/030-F; F.S.-O.), the Swedish Medical
Research Council (2010-3462; A.A.), the Swedish Cancer Society
(Cancerfonden, 12-0676; A.A.), and the Swedish Childhood Cancer
Foundation (PROJ08/015; A.A.).