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A HLA-A2 restricted human CTL line recognizes a novel tumor cell expressed p53 epitope

✍ Scribed by Peter A. Würtzen; Mogens H. Claesson

Publisher
John Wiley and Sons
Year
2002
Tongue
French
Weight
129 KB
Volume
99
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

A p53 peptide‐specific CTL line was generated through stimulation with autologous monocyte‐derived dendritic cells (DC) pulsed with wild‐type HLA‐A2 binding p53 derived peptides. A p53 peptide‐specific CD8^+^ CTL line was established from a healthy HLA‐A2 positive donor. The CTL line was characterized with respect to specificity, affinity and killing of cell lines derived from p53 mutated spontaneous tumors. The CTL line demonstrated lysis of p53~139–147~ pulsed target cells and cold target inhibition experiments as well as antibody blocking confirmed that the killing was epitope‐specific, HLA‐A2 restricted and dependent on CD8‐binding. Interestingly, the affinity of the CTL line was only in the micromole per liter range and target cells pulsed with less than 0.01 μM peptide were not recognized. Furthermore, 3 HLA‐A2^+^ p53 mutated tumor cell lines were efficiently lysed by the CTL line, indicating that this novel p53 peptide epitope is endogenously processed and presented by the HLA‐A2 molecules of the tumor cells. In conclusion, CTL reactivity towards a wild‐type p53 peptide was revealed through induction with DC pulsed with a pool of HLA‐A2 binding p53 peptides. In addition, the CTL line, which expressed relatively low affinity for the HLA‐A2/peptide complex, was able to kill 3 different HLA‐A2^+^ p53 mutated tumor cell lines. The present and our previous observations expand the number of p53‐derived peptides suitable for vaccination protocols for cancer patients with p53 positive tumors. © 2002 Wiley‐Liss, Inc.

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