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International Immunology, Vol. 12, No. 9, 1217-1225, September 2000
© 2000 Japanese Society for Immunology

The epitope detected by cytotoxic T lymphocytes against thymus leukemia (TL) antigen is TAP independent

Kunio Tsujimura1, Yuichi Obata1, Shigeru Iwase1,2, Yasue Matsudaira1, Satoshi Ozeki1 and Toshitada Takahashi1

1 Laboratory of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
2 Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

Correspondence to: K. Tsujimura

Thymus leukemia (TL) antigens belong to the family of MHC class Ib antigens. We have shown in our previous studies that they serve as transplantation antigens, and can be recognized by both TCR {alpha}ß and TCR {gamma}{delta} cytotoxic T lymphocytes (CTL) with TL but not H-2 restriction. Although TL are known to be expressed TAP independently, it is unclear whether peptide loading on TL molecules is necessary for the formation of CTL epitopes. In the present study, we first showed that TL expression is ß2-microglobulin (ß2m)-dependent but TAP1 independent by flow cytometric analysis of thymocytes from ß2m- or TAP1-deficient mice crossed with TL transgenic mice expressing Tlaa-3-TL on their thymocytes. Subsequently, we investigated the epitope recognized by CTL derived from C3H mice immunized with skin from a transgenic mouse expressing T3b-TL ubiquitously. Bulk CTL lines against TL from primary mixed lymphocyte cultures showed comparable cytotoxicity against T3b-TL transfectants of TAP2-deficient murine RMA-S grown at 37°C to that against those grown at 25°C. Furthermore, TCR {alpha}ß and TCR {gamma}{delta} CTL clones against TL recognized TL expressed on T3b-TL transfectants of RMA-S and Drosophila melanogaster cells having broad defects in peptide loading of MHC, and lysed these target cells. These results together indicate that TL-specific CTL populations primarily recognize epitopes expressed TAP independently.

Keywords: MHC class Ib, thymus leukemia (TL) antigen

Transmitting editor: K. Okumura


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