Detection of non-HLA antigens: effect of lymphocyte priming and amplification signals

We studied three potential mechanisms that might account for the difficulty in detecting non-HLA antigenic disparities between HLA-identical siblings: (1) a low frequency of antigen-reactive cells; (2) the failure of antigen recognition to trigger proliferation or cytotoxicity; and (3) the development of suppressor cells or factors. In vitro sensitization was used to increase the frequency of antigen-reactive cells. Allogeneic lymphocytes or supernatants from mixed lymphocyte cultures were used to provide nonspecific proliferative signals. Neither approach was successful in facilitating the detection of proliferation or cytotoxicity between HLA-identical siblings. Furthermore, we found no evidence for the development of antigen-specific suppressor cells or factors. These data indicate that other mechanisms must underlie the difficulty in detecting non-HLA antigens in vitro.