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 Cr‐release or interferon‐Γ 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‐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.