Open AccessNatural Antigenic Peptides from Squamous Cell Carcinoma Recognized by Autologous HLA‐DR8–restricted CD4 + T Cells
Author(s) -
Kondo Hiroaki,
Sahara Hiroeki,
Miyazaki Akihiro,
Nabeta Yuki,
Hirohashi Yoshihiko,
Kanaseki Takayuki,
Yamaguchi Akira,
Yamada Naoyuki,
Hirayama Kazuo,
Suzuki Manabu,
Hamuro Junji,
Torigoe Toshihiko,
Takahashi Nobuaki,
Kohama Geniku,
Ikeda Hideyuki,
Sato Noriyuki
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01338.x
Subject(s) - cytotoxic t cell , human leukocyte antigen , cd8 , microbiology and biotechnology , antigen , chemistry , cell culture , biology , biochemistry , in vitro , immunology , genetics
A large number of human tumor antigens recognized by CD8 + cytotoxic T lymphocytes (CTL) have been identified. Some of them have been employed in clinical trials and have achieved some objective responses. However, little is known about those that are recognized by CD4 + T cells, except for a very few that were identified from melanomas. Previously, we reported that an oral squamous cell carcinoma (SCC) cell line, OSC–20, was effectively lysed by HLA‐DRB1·08032 (HLA‐DRS)‐restricted autologous CD4 + T cell line, TcOSC–20. In this study, we performed two steps of chromatographic purification of the tumor cell lysate in combination with mass spectrometry. We found one reverse‐phase high‐performance liquid chromatography (RP‐HPLC) fraction that was effectively recognized by the T cells. We analyzed the fraction by nano‐liquid chromatography/electrospray ionization ion trap mass spectrometry (LC/MS/MS) and found six representative ions. We could determine the primary amino acid sequence of each of the six ions. Three of them contained a potential HLA‐DR8 binding motif, and TcOSC–20 showed a rather strong cytotoxic response to one of the synthetic pep tides, namely, amino acid residues 321–336 of human a‐enolase. Thus, several gene products of squamous cancer cells are endogenously processed and may be presented on HLA class II molecules, so that they could constitute target molecules for autologous CD4 + T cells.