Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome

Eur J Immunol. 2001 Feb;31(2):563-72. doi: 10.1002/1521-4141(200102)31:2<563::aid-immu563>;2-d.


Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Calcium-Binding Proteins / immunology*
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte*
  • Eye Proteins*
  • HLA-A Antigens / analysis
  • HLA-A24 Antigen
  • Hippocalcin
  • Humans
  • Immunotherapy
  • Lipoproteins*
  • Neoplasms / therapy
  • Nerve Tissue Proteins*
  • Paraneoplastic Syndromes / immunology*
  • Prognosis
  • Recoverin
  • Retinal Diseases / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, Neoplasm
  • Calcium-Binding Proteins
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Eye Proteins
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Lipoproteins
  • Nerve Tissue Proteins
  • RCVRN protein, human
  • Recoverin
  • Hippocalcin