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T cell recognition of melanoma antigens in association with HLA-A1 on allogeneic melanoma cells

  • Original Articles
  • Interleukin-4, HLA-A1, T Cell Cytokines, HLA Restriction, T Cell Cloner, Cytotoxic T Cells, Melanoma
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Previous studies have shown that recognition of melanoma by cytotoxic T lymphocytes may be restricted by HLA-A1, A2 and other HLA antigens. The present study examined the cytotoxic specificity and major histocompatibility complex restriction of cloned cytotoxic T lymphocytes (CTL) isolated from a patient with the HLA phenotype A3,31 who had been immunized with a vaccine prepared from HLA-A1,3 melanoma cells. Cytotoxic assays against HLA-typed allogeneic melanoma cells indicated that cloned CTL from the patient were able to kill allogeneic melanoma cells expressing HLA-A1 but not other HLA-A1-positive cells. Studies on a representative clone indicated that proliferation and cytokine (tumour necrosis factor α) production in response to melanoma cells was also associated with HLA-A1 on melanoma cells. Response to the melanoma cells was associated with interleukin-4 (IL-4) rather than IL-2 production. The antigen recognized in the context of HLA-A1 on allogeneic melanoma cells was detected in cytotoxic assays on cells from 9 of 12 HLA-A1+ melanoma cell lines and did not appear to be the product of the MAGE-1 or-3 genes. These findings suggest that T cells can recognize melanoma antigens in the context of alloantigens and that allogeneic vaccines containing “immunodominant” alloantigens may generate CTL that are ineffective against autologous melanoma. The study does not, however, exclude the possibility that CTL with specificity to the latter may be activated by allogeneic vaccines, and further studies are needed to answer this question.

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Authors and Affiliations

  1. Oncology and Immunology Unit, Royal Newcastle Hospital, Room 443, David Maddison Clinical Science Building, 2300, Newcastle, NSW, Australia

    Qiyuan Chen, Melanie Smith, Tam Nguyen & Peter Hersey

  2. Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, PO Box Royal Melbourne Hospital, Melbourne, Victoria, Australia

    Darryl W. Maher

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  1. Qiyuan Chen
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  2. Melanie Smith
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  3. Tam Nguyen
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  4. Darryl W. Maher
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Chen, Q., Smith, M., Nguyen, T. et al. T cell recognition of melanoma antigens in association with HLA-A1 on allogeneic melanoma cells. Cancer Immunol Immunother 38, 385–393 (1994). https://doi.org/10.1007/BF01517208

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  • DOI: https://doi.org/10.1007/BF01517208

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