Abstract
A CD8+ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood mononuclear cells of a patient with primary melanoma. The CD8+ CTL line specifically lysed the autologous primary melanoma cells and not the natural killer cell-sensitive K562 cells or lymphokine activated killer cell-sensitive DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and -unmatched allogeneic melanoma, glioma, breast and colorectal carcinoma cells was tested as targets in cytolysis assays, 4 HLA-matched and two HLA-unmatched allogeneic metastatic melanoma lines were lysed by the CD8+ CTL. Lysis of autologous and allogeneic melanoma cells was dependent on the effector-to-target cell ratio. Lysis of autologous melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell receptor) dependent and FAS-FAS-L, and CD1 independent. Identification of the melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a vaccine for a broad population of melanoma patients.
Highlights
Cytotoxic T lymphocytes (CTL) have been established from various lymphoid sources of patients with metastatic melanoma[1]
human leukocyte antigen (HLA)-unrestricted CTL from ovarian, breast and pancreatic carcinoma patients have been reported and they are known to recognize epitopes of mucin (MUC1) tumorassociated antigen [15,16,17]. It is unclear whether the CTL against melanomas and carcinomas are truly HLA-unrestricted, as target cells were not fully HLA subtyped [3,4,5,6] and high E:T cell ratios were used in cytolysis assays [5,6]
Our study provides strong evidence that the cytolytic activity of the CD8+ 793 CTL line is HLA-unrestricted
Summary
Cytotoxic T lymphocytes (CTL) have been established from various lymphoid sources of patients with metastatic melanoma[1]. The majority of CTL are of CD8 phenotype and generally lyse tumor cells in a human leukocyte antigen (HLA)-restricted manner. CD8+ CTL that recognized and lysed melanoma targets of various HLA types have been described [3,4,5,6] It is unclear whether the CTL are truly HLA-unrestricted, as the allogeneic tumor target cells used were not fully HLA subtyped [3,4,5,6] and, partial HLA matching of these targets with the CTL cannot be excluded with certainty. The demonstration of the absence of HLA restriction was based on the absence of CTL lysis blocking in the presence of high concentrations of anti-HLA antibodies. The lysis of the autologous or allogeneic tumor cells was not blocked by monoclonal antibodies (MAbs) to HLA-class I or class II, confirming that the CTL lyse targets in a HLA-unrestricted manner
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