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Keywords:

  • cytotoxic T lymphocytes;
  • HLA-A24;
  • squamous cell carcinoma;
  • T-cell receptor;
  • tumor antigen

Abstract

We recently described that the SART-1690–698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1math image tumor cells from peripheral blood mononuclear cells (PBMCs) of HLA-A24+ cancer patients. In our study, in 5 of 14 HLA-A24+ patients with oral squamous cell carcinomas (SCCs), CTLs could be induced with the SART-1690–698 peptide from the PBMCs. In 2 of the patients from whom the highest CTL activities were induced, the T-cell receptor (TCR) Vβ repertoire expressed by the SART-1690–698-specific CTLs was found to be restricted and multiple Vβ families were predominantly expressed in each patient. Although the predominant Vβ families were different between the 2 patients, Vβ7 was highly and commonly predominant. The same predominant Vβ families were also detected in the tumor-infiltrating lymphocytes (TILs) from each patient, and each Vβ family contained one or more unique T-cell clonotypes. The unique T-cell clonotypes were found to be common between the TILs and SART-1690–698-specific CTLs from each patient, and especially 2 T-cell clonotypes with Vβ7 were identical even in the 2 patients. One of the 2 T-cell clonotypes with Vβ7 was detected in the TILs from 11 of 14 HLA-A24+ patients and another was found in those from 8 of HLA-A24+ patients, while none of 10 HLA-A24 patients demonstrated both T-cell clonotypes. These results strongly suggest that the T-cell clonotypes with Vβ7 are major TCR Vβ genes expressed by SART-1690–698-specific CTLs. Furthermore, autologous tumor cells from one of the HLA-A24+ patients stimulated the PBMCs and regional lymph node cells (LNCs) to expand the same T-cell clonotypes as those in the SART-1690–698-specific CTLs. These results strongly suggest that the SART-1690–698-specific CTLs clearly accumulate in vivo, especially in the TILs, as a consequence of in situ antigenic stimulation by autologous tumor cells. The identification of the unique TCR Vβ genes used by SART-1259-specific CTLs should help to improve the diagnosis of the specific immune response in patients with SART-1math image cancers, especially during anticancer immunotherapy. © 2003 Wiley-Liss, Inc.