Accumulation of low-avidity anti-melanocortin receptor 1 (anti-MC1R) CD8+ T cells in the lesional skin of a patient with melanoma-related depigmentation.
Melanoma Res
; 16(2): 165-74, 2006 Apr.
Article
en En
| MEDLINE
| ID: mdl-16567972
Spontaneous or therapy-induced depigmentation in patients with melanoma has long been considered a favourable prognostic indicator. In this report, we isolated T cells infiltrating the depigmented skin of an HLA-A2+/DR4+ patient with melanoma, and detected a very high frequency of CD8+ T cells specific for melanocortin receptor 1 (MC1R), a hormone receptor involved in cutaneous pigmentation. In particular, tissue-infiltrating CD8+ T cells dominantly recognized the novel MC1R52-60 peptide epitope in an HLA-A2-restricted manner, and peptide-reactive CD8+ T cells were also detected in freshly isolated peripheral blood from this patient. Although type 1 CD4+ T-cell responses against MC1R were not detected in fresh tissue isolates, short-term in-vitro stimulation of peripheral blood lymphocytes resulted in the rapid expansion of CD4+ T cells reactive against novel HLA-DR4-presented epitopes derived from the MC1R protein (i.e. MC1R82-95, MC1R105-118 and MC1R149-161). MC1R peptide-specific CD8+ T-cell clones isolated from the depigmented skin of this patient were characterized by comparatively low functional avidity for specific major histocompatibility complex-peptide complexes and were poorly lytic; however, these effector cells were capable of secreting both interferon-gamma and granzyme B against relevant target cells in vitro, and may have played an important role in the induction of leucoderma in situ in this patient.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Hipopigmentación
/
Linfocitos T CD8-positivos
/
Receptor de Melanocortina Tipo 1
/
Melanoma
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido