Genetic immunization maps T cell (auto)immune responses to self antigens homologous to exogenous proteins

Genetic immunization represents a new tool for investigating physiological and pathological immune responses. Here we used genetic immunization with naked DNA to study the immune relevance of aminoacid sequence homologies by evaluating the outcome of immunization to a viral protein homologous to an HLA molecule. The viral protein was Balf2, a protein of Epstein-Barr virus (EBV) that shares aminoacid sequence homology with the HLA allele DRB1*0801. After genetic immunization of BALB/c mice with a construct encoding Balf2, we analyzed T cell responses of immunized mice. We found that cross-reactive proliferative and cytotoxic responses were raised to the homologous sequence as expressed by HLA-DRB1*0801. Furthermore, preferential secretion of Th1-type pro-inflammatory cytokines occurred. This strategy can allow rapid screening of interactive immune networks involving aminoacid sequence homologies between organisms.