Establishment and Epitope Analysis of Allo-Specific Cytotoxic T Lymphocytes at a Tumor Site Recognizing a Spouse's HLA-A0206 Molecule

PROBLEM: The molecular basis of allo-reactivity in reproductive immunity has not been fully clarified. METHOD OF STUDY: Cytotoxic T lymphocytes (CTLs) were established from tumor-infiltrating lymphocytes (TILs). The allo-reactivity of the CTLs against various tumor cell lines or human leukocyte antigen (HLA)-A allele-transfected COS-7 cells was measured by 51 Cr-release or interferon-γ production assay. RESULTS AND CONCLUSIONS: We have established CTLs reacting to an HLA-A()2()6 molecule that matched a spouse's HLA-A allele from the TILs of a 68-year-old multiparous patient with gastric cancer. The amino acids at positions 66 and 88 in the α1 domain of HLA-A0206, both of which were common in the other HLA-A2 subtypes, were involved in the recognition by the CTLs. Endogenous peptides in the groove were not involved in the recognition. These results suggest the presence of long-lasting memory CTLs raised by the reproduction process, and may facilitate a better understanding of the molecular basis of allo-recognition during reproduction.