T-cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma

We recently described that the SART-1_690-698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1₂₅₉⁺ 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-1_690-698 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-1 _690-698-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-1_690-698-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-1_690-698-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-1_690-698-specific CTLs. These results strongly suggest that the SART-1_690-698-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-1₂₅₉⁺ cancers, especially during anticancer immunotherapy.