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Generation and evaluation of the efficacy of rhesus monkey soluble cytotoxic T lymphocyte-associated antigen-4 in the allogeneic mixed lymphocyte reaction |
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| Authors: | Jung-Sik Kim Inho Choi Han-Hyoung Lee Suk Jun Lee Manheum Na Sang-Hoon Kim Jihye Han Joonbeom Bae Sang-Pil Choi Sang Joon Kim Chung-Gyu Park Taehoon Chun |
| Institution: | 2. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea 3. Xenotransplantation Research Center, Seoul National University Hospital, Seoul, 110-799, Republic of Korea 4. School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Republic of Korea 1. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea 5. Department of Surgery, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea |
| Abstract: | Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is a transmembrane protein that is structurally similar to CD28. As CTLA-4 has a much higher binding affinity to B7 than CD28, several approaches using soluble CTLA-4 have been tried to down-regulate T cell activity by blocking the interaction between CD28 and B7. We constructed soluble rhesus monkey CTLA-4 immunoglobulin (CTLA-4Ig) containing a critical binding site to B7 combined with a constant Ig heavy chain region in a mammalian system. Flow cytometry analyses indicated that soluble rhesus monkey CTLA-4Ig bound to rhesus monkey CD86 (B7.2). Moreover, soluble rhesus monkey CTLA-4Ig more effectively blocked the rhesus monkey–rhesus monkey allogeneic mixed lymphocyte reaction compared with that of humans. These results indicate that soluble rhesus monkey CTLA-4Ig may be useful in preclinical trials in a rhesus monkey model. |
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