T cell immune responses against melanoma and melanocytes in cancer and autoimmunity

Yutaka Kawakami, Yuriko Suzuki, Tomoko Shofuda, Yukiko Kiniwa, Takashi Inozume, Katsuaki Dan, Toshiharu Sakurai, Tomonobu Fujita

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

T cell responses specific for melanoma cells and melanocytes appear to be involved in the rejection of melanoma tumors, as well as in the development of autoimmune reactions in patients with Vogt-Koyanagi-Harada disease (VKH), sympathetic ophthalmia, or autoimmune vitiligo. Some of the target antigens for those T cells have been isolated using cDNA expression cloning with melanoma reactive T cells derived from tumor infiltrating lymphocytes (TIL) of patients with melanoma. These include melanocyte specific proteins, such as tyrosinase, TRP1, TRP2, gp100, and MART-1, cancer-testis antigens, and mutated peptidcs derived from genetic alterations in melanoma cells. Some of the melanoma reactive T cells appear to respond to cryptic or subdominant self epitopes in melanosomal proteins. Modification of those epitopes to increase their immunogenicity by replacement of amino acids at primary anchor residues for peptide/MHC binding, allowed an improvement in immunotherapy for patients with melanoma. Targets for autoreactive T cells against melanocytes in those autoimmune disorders remain to be identified. Isolation of novel target antigens is important for understanding these pathological T cell responses, as well as for developing new diagnostic and treatment methods for these diseases. A variety of techniques, including cDNA expression cloning with T cells, serological analysis of recombinant cDNA expression libraries (SEREX), cDNA subtraction with representational differential analysis (RDA), and serial analysis of gene expression (SAGE) are now being applied to identify novel melanoma/melanocyte antigens recognized by T cells and antibodies.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalPigment Cell Research
Volume13
Issue numberSUPPL. 8
DOIs
Publication statusPublished - 2000

Keywords

  • Autoantigens
  • Cryptic self epitopes
  • Tumor antigens
  • VKH
  • Vitiligo

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Developmental Biology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Kawakami, Y., Suzuki, Y., Shofuda, T., Kiniwa, Y., Inozume, T., Dan, K., Sakurai, T., & Fujita, T. (2000). T cell immune responses against melanoma and melanocytes in cancer and autoimmunity. Pigment Cell Research, 13(SUPPL. 8), 163-169. https://doi.org/10.1034/j.1600-0749.13.s8.29.x