Anti-tumor vaccination in heterozygous congenic F1 mice: Presentation of tumor-associated antigen by the two parental class I alleles

Peptide vaccination of homozygous mice against syngeneic tumors using singl e major histocompatibility complex (MHC) class I-restricted cytotoxic T lym phocyte (CTL) epitopes elicits effective immune responses against metastati c growth. So far, single-peptide vaccination of patients against their auto logous rumors seems to elicit less satisfactory results. In this study, the authors tried to determine whether effective anti-metastatic immunity requ ires the presentation of peptides restricted by the two parental class I ma jor histocompatibility complex alleles in heterozygous hosts. The immune re sponse against the H-2(b)-derived 3LL Lewis lung carcinoma was evaluated in heterozygous recombinant congenic F1 mice (K-k x K-b) and (K-d x K-b). Vac cination of such heterozygous animals with dendritic cells expressing the t wo parental H-2K alleles, pulsed with total tumor extract, elicited a poten t anti-metastatic response. A comparable response was obtained after vaccin ation with tumor cells genetically modified to express the two class I alle les. In contrast, vaccination of the heterozygous mice with dendritic cells expressing only one of the parental F1 H-2K alleles or with rumors express ing only one H-2K allele failed to elicit effective immunity against tumor metastasis in recombinant congenic F1 mice. It appears, therefore, that to achieve effective anti-metastatic immunotherapy in heterozygous organisms, presentation of cytotoxic T lymphocyte epitopes restricted by the two paren tal class 1 alleles is required.