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 ha s 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 v arious tumor cell lines or human leukocyte antigen (HLA)-A allele-transfect ed COS-7 cells was measured by Cr-51-release or interferon-gamma production assay. RESULTS AND CONCLUSIONS: We have established CTLs reacting to an HLA-A0206 molecule that matched a spouse's HLA-A allele from the TILs of a 68-year-ol d multiparous patient with gastric cancer. The amino acids at positions 66 and 88 in the ctl domain of HLA-A0206, both of which were common in the oth er HLA-A2 subtypes, were involved in the recognition by the CTLs. Endogenou s peptides in the groove were not involved in the recognition. These result s suggest the presence of long-lasting memory CTLs raised by the reproducti on process, and may facilitate a better understanding of the molecular basi s of allo-recognition during reproduction.