Analysis of the alloreactive T cell repertoire in man. I. Differences in precursor frequency for cytotoxic T cell responses against allogeneic MHC molecules in unrelated individuals.

Abstract

We demonstrate here that in man the frequency of cytotoxic T cells specific for a given set of allo-major histocompatibility complex (MHC) antigens varies among unrelated individuals. This has been established by limiting dilution analysis of human peripheral blood lymphocytes (HPBL) in the presence of irradiated autologous filler cells, T cell growth factors, and irradiated HPBL carrying allo-MHC antigens. Two unrelated individuals were tested against the same panel of allo-MHC antigens. We have been able to identify frequencies of T cells ranging from 1:5,000 to 1:20,000(high), 1:20,000 to 1:60,000(intermediate) and 1:60,000 to 1:100,000(low). In some cases, the precursor frequency of cytotoxic T cells was so low that it was considered to represent nonresponsiveness. The clear differences in precursor frequency suggest that this system is suitable for further analysis of the allo-MHC-specific repertoire in man.