Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients

Palermo, Belinda; Campanelli, Rita; Mantovani, Stefania; Lantelme, Erica; Manganoni, Ausilia Maria; Carella, Graziella; Prada, GA Da; Cuna, G. Robustelli della; Romagné, François; Gauthier, Laurent; Necker, Antje; Giachino, Claudia

doi:10.1002/1521-4141(200102)31:2<412::aid-immu412>3.0.co;2-4

Cited by 39 publications

(37 citation statements)

References 40 publications

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“…The average numbers of circulating A2/Melan-A tetramer + T cells enumerated ex vivo in the melanoma and vitiligo patients studied in the present paper were found to be highly comparable. These cell frequency data fit in well with our previous analyses of other HLA-A*0201 melanoma and vitiligo patients [13,14] and are in agreement with the estimates reported in the literature [5,8,9]. The in vivo priming and functional capacity of melanocyte-specific lymphocytes are important issues, since recent data suggested that Melan-Aspecific cells circulating in some melanoma patients are either ignorant (not primed) or anergic [8,23,24].…”

Section: Discussionsupporting

confidence: 90%

“…Melan-A-specific T cell clones, five from vitiligo and five from melanoma, previously obtained by limiting dilution from Melan-A-sensitized T cell lines [13,14], were assayed for their TCR affinity. TCR affinity was defined through tetramer binding analyses, as described [19][20][21][22].…”

Section: Tumor Reactivity Of Whole Melan-a-specific Cytotoxic T Lymphmentioning

confidence: 99%

“…We found that the tetramer label decayed with t 1/2 = 3.6 h in the T cell clone from melanoma, but it decayed at a sixfold slower rate, with t 1/2 = 24 h, in the T cell clone from vitiligo, demonstrating a highly increased stability of the TCR-tetramer complexes in the latter. Functional activity of these clones has been previously assessed by testing their ability to lyse two different Melan A + , HLA-matched melanoma cell lines in chromium-release assays [13,14] and the corresponding results are summarized here in order to allow a direct comparison (Fig. 4C).…”

Section: Tumor Reactivity Of Whole Melan-a-specific Cytotoxic T Lymphmentioning

confidence: 99%

“…Notably, however, cells from vitiligo patients were capable of lysing HLA-matched melanoma cell lines much more efficiently than CTL obtained from melanoma patients [13][14][15]. In this paper, we have performed for the first time a direct comparison of whole melanocyte-specific T cell populations in the two diseases.…”

Section: Introductionmentioning

confidence: 99%

“…By the use of HLA class I/epitope tetramers, a tool to measure the frequency of specific CTL precursors independently of their functional state [12], our group already contributed to the demonstration that melanocyte-specific CTL are present in the peripheral blood of both melanoma and vitiligo patients [13][14][15][16]. Notably, however, cells from vitiligo patients were capable of lysing HLA-matched melanoma cell lines much more efficiently than CTL obtained from melanoma patients [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo

et al. 2005

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Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: Cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor downregulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-c production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocytespecific cytotoxic responses differs between the two pathologies.

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