Expression of fetal antigens by normal human skin cells grown in tissue culture

Normal and malignant tissue culture cells are commonly used in studies of the immune response to human tumors, In the course of studies of the humoral immune response to human osteo sarcoma, it was observed that 7 of 8 patients demonstrated serum reactivity both preoperatively (tumor bearing) and postoperatively (non-tumor bearing) to autochthonous sarcoma cells in tissue culture. However, these same sera were equally capable of lysing autochthonous normal skin cells in tissue culture. Therefore, 155 allogeneic human sera from normal individuals with no history of cancer were tested for lytic reactivity against multiple normal human skin lines grown in tissue culture. In all, 103 (66%) of these sera demonstrated this reactivity. These lytic antibodies against determinants on normal human skin in tissue culture were present more frequently in younger individuals and obscured attempts to serologically identify cell surface antigens directed against human tumor-specific antigens. The authors, therefore, sought to identify these 'neo-antigens' present on normal tissue culture cells. It is known that normal human sera may cause complement-mediated lysis of normal human skin cells grown in tissue culture. This lytic reactivity can be completely removed by absorption with first trimester fetal tissue. Absorption with a variety of normal adult human tissues including lymphocytes, decidua, skin, and muscle are incapable of absorbing reactivity. Absorption of reactivity by fetal tissue is specific and not due to the introduction of anti-complementary or other nonspecific factors, as evidenced by the inability of simultaneous fetal absorption to remove reactivity from antisera with specificity for HLA antigens. Similarly, absorption of lytic sera with fetal calf serum proteins was incapable of removing reactivity against normal cells in tissue culture. It thus appears that normal human cells in tissue culture express antigens shared by the first trimester human fetus, which are present on a variety of adult human tissues. This 'neoantigen' present on normal human cells when grown in tissue culture is a potential source of confusion and must be accounted for in searching for human tumor-specific antigens utilizing tissue culture cells.