Accumulation of low-avidity anti-melanocortin receptor 1 (anti-MC1R) CD8+ T cells in the lesional skin of a patient with melanoma-related depigmentation.
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.
Wankowicz-Kalinska
Anna
A
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Mailliard
Robbie B
RB
Olson
Kathleen
K
Graham
Fiona
F
Edington
Howard
H
Kirkwood
John M
JM
Martinek
Stephanie
S
Das
Pranab K
PK
Storkus
Walter J
WJ
D000328:Adult; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D017496:Hypopigmentation / Q000209:etiology / Q000276:immunology*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D010257:Paraneoplastic Syndromes / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D044102:Receptor, Melanocortin, Type 1 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D044102:Receptor, Melanocortin, Type 1