The Intronic Region of an Incompletely Spliced gp100 Gene Transcript Encodes an Epitope Recognized by Melanoma-Reactive Tumor-Infiltrating Lymphocytes

Paul F. Robbins, Mona El-Gamil, Yong F. Li, Ellen B. Fitzgerald, Yutaka Kawakami, Steven A. Rosenberg

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Abstract

Recent studies have characterized a number of the Ags that are recognized by melanoma-reactive T cells. Although the majority of tumor Ags appear to represent nonmutated gene products, a variety of epitopes have been shown to arise from either mutated or alternatively processed transcripts. Here, we report that the screening of a cDNA library with a HLA-A24-restricted melanoma-reactive T cell cloid derived from tumor infiltrating lymphocytes resulted in the isolation of a variant of the gp100 gene that had retained the entire fourth intron of this gene, termed gp100-in4. The gp100-in4 transcript could be detected by reverse transcriptase-PCR but could not be detected in Northern blots conducted with melanoma RNA, indicating that it represents a relatively rare transcript. Read-through of this transcript into the region corresponding to the fourth intron gave rise to an additional 35 amino acids not found in the normal gp100 glycoprotein, and a peptide within this region conforming to the HLA-A24 consensus motif (VYFFLPDHL) was shown to be recognized by the T cell cloid. The sequence of the intron was identical with that of a previously isolated genomic gp100 clone, and T cells that recognized the gp100-in4 gene product were found to recognize HLA-A24-matched allogeneic melanoma cell lines and melanocytes, demonstrating that this represents a nonmutated epitooe. These results further extend the types of Ags that can be recognized by melanoma-reactive T cells to aberrant transcripts of melanosomal genes.

Original languageEnglish
Pages (from-to)303-308
Number of pages6
JournalJournal of Immunology
Volume159
Issue number1
Publication statusPublished - 1997 Dec 1

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Robbins, P. F., El-Gamil, M., Li, Y. F., Fitzgerald, E. B., Kawakami, Y., & Rosenberg, S. A. (1997). The Intronic Region of an Incompletely Spliced gp100 Gene Transcript Encodes an Epitope Recognized by Melanoma-Reactive Tumor-Infiltrating Lymphocytes. Journal of Immunology, 159(1), 303-308.