TCR Vβ3+ and Vβ6+ CTL recognize tumor-associated antigens related to HER2/neu expression in HLA-A2+ ovarian cancers

George E. Peoples, Ichiro Yoshino, Cara C. Douville, J. Valerie Ravon Andrews, Simon Goedegebuure, Timothy Eberlein

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34 Scopus citations

Abstract

We have recently shown that HLA-A2-restricted, tumor-specific CTL can be isolated from tumor-infiltrating lymphocytes (TIL) in ovarian cancer, and that the sensitivity of ovarian tumors to these CTL is correlated with HER2/neu expression. Furthermore, utilizing PCR, we have documented previously that Vβ2, Vβ3, Vβ6, and Vβ7 are represented in increased proportions in ovarian tumor-specific CTL lines. Therefore, to correlate the interaction of these specific TCR Vβ segments with the HLA-A2 molecule and potential tumor-associated Ags (TAA) related to HER2/neu expression, we have utilized available mAbs to Vβ2, Vβ3, and Vβ6. We found that Vβ2+, Vβ3+, and Vβ6+ CTL mediate antitumor activity, and a combination of these mAbs resulted in 83 to 95% inhibition of the cytotoxicity against autologous tumor from three separate patients. These mAbs also were capable of blocking HLA-A2-matched allogeneic cytotoxicity, suggesting that all three Vβ families recognize TAA in the context of HLA-A2. An HLA-A2+ melanoma was transfected with the HER2/neu gene and became sensitive to HLA-A2+ ovarian cancer-specific CTL lysis. This cytotoxicity was mediated by Vβ3+ and Vβ6+ CTL, as demonstrated by mAb-blocking studies. FACS-depletion studies confirmed that CTL populations depleted of Vβ3 or Vβ6 no longer could recognize the HER2/neu transfectant. We conclude that Vβ3 and Vβ6 recognize some TAA that are either derived from the HER2/neu protein or induced by the expression of the HER2/neu gene and presented in the context of HLA-A2. Furthermore, Vβ2 seems to recognize an HER2/neu-unrelated Ag system also presented by HLA-A2.

Original languageEnglish
Pages (from-to)4993-4999
Number of pages7
JournalJournal of Immunology
Volume152
Issue number10
StatePublished - May 15 1994

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