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Affinity, specificity and T‐cell‐receptor diversity of melanoma‐specific CTL generated in vitro against a single tyrosinase epitope
Author(s) -
Visseren Marjan J.W.,
van der Burg Sjoerd H.,
Hawes Gail E.,
van der Voort Ellen I.H.,
van den Elsen Peter J.,
Melief Cornelis J.M.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970917)72:6<1122::aid-ijc30>3.0.co;2-3
Subject(s) - ctl* , cytotoxic t cell , biology , priming (agriculture) , ex vivo , antigen , clone (java method) , t cell receptor , epitope , melanoma , immunology , in vitro , cancer research , in vivo , immunotherapy , immune system , t cell , microbiology and biotechnology , cd8 , gene , biochemistry , botany , germination
MHC‐class‐I‐restricted cytotoxic T lymphocytes (CTL) specific for tumor‐associated antigens expressed by malignant cells are important components of the immune response against cancer. Recently, tumor‐specific CTL could be generated in vitro, with responding lymphocytes from the blood of healthy blood donors. In the present study, we confirm that peptide‐specific stimulation in vitro can induce high‐affinity CTL capable of recognizing tumor cells expressing the appropriate tumor antigen. These tyrosinase‐specific CTL display a restricted usage of TCRAV and TCRBV gene segments but of diverse CDR3 regions, resulting in a distinct fine‐specificity for each CTL clone. This suggests that, similar to in vivo priming, peptide‐pulsed APC are capable of stimulating a T‐cell response in vitro expressing a limited TCR repertoire against autologous tumors. The generated CTL can recognize their target structure with high affinity, and this correlates in part with tumor‐cell lysis. This methodology may be used to treat melanoma patients with infusion of ex vivo ‐induced and ‐expanded CTL. Int. J. Cancer 72:1122–1128, 1997. © 1997 Wiley‐Liss, Inc.