Frequent detection of anti-recoverin cytotoxic T-lymphocyte precursors in peripheral blood of cancer patients by using an HLA-A24-recoverin tetramer.
Recoverin is a photoreceptor-specific calcium binding protein that is only expressed in the retina in normal tissues. Aberrant expression of recoverin, however, has been observed in several cancer tissues and may cause a very rare autoimmune disease, cancer-associated retinopathy (CAR). It has been suggested that CAR-positive cancer patients have a more favorable prognosis than CAR-negative cancer patients. To estimate the status of recoverin-specific T cells in such cancer patients, we generated an HLA-A24-recoverin peptide tetramer. By use of the tetramer, we could directly assess the frequency of CTL precursors (CTLp) of 20 HLA-A24(+) cancer patients with ten colon, six stomach and four breast cancers, and seven healthy individuals. Four cancer patients showed a CTLp frequency higher than 0.9%. Seven cancer patients including the former four patients and two healthy individuals showed specific anti-recoverin cytotoxic responses in an HLA-A24-restricted manner after in vitro stimulation with the recoverin peptide. Moreover, five cancer patients analyzed in an independent experiment using different peripheral blood mononuclear cells (PBMC) samples showed similar CTLp and cytotoxic T lymphocyte (CTL) frequencies and cytotoxic responses, suggesting that the CTLp frequency analyzed by the tetramer and the cytotoxic response may have a good correlation. Thus, we hypothesize that anti-recoverin CTLp may exist in some cancer patients, and that anti-recoverin CTL may be readily induced.
Rong
Shunshui
S
Department of Pathology, Sapporo Medical University School of Medicine, Minami-1-jo, Nishi-17-chome, Chuo-ku, Sapporo 060-8556, Japan.
Ikeda
Hideyuki
H
Sato
Yuriko
Y
Hirohashi
Yoshihiko
Y
Takamura
Yukio
Y
Sahara
Hiroeki
H
Sato
Takashi
T
Maeda
Akiko
A
Ohguro
Hiroshi
H
Sato
Noriyuki
N
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000276:immunology; D002469:Cell Separation; D005136:Eye Proteins; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000737:chemistry*; D059871:HLA-A24 Antigen; D051597:Hippocalcin; D006801:Humans; D008074:Lipoproteins; D008545:Melanoma / Q000276:immunology; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000276:immunology; D009419:Nerve Tissue Proteins; D010455:Peptides / Q000737:chemistry; D051603:Recoverin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D010455:Peptides; C496731:RCVRN protein, human; D051603:Recoverin; D051597:Hippocalcin