Sensitization of human lymphocytes in vitro: genetic restriction of secondary T cell responses is dictated by the HLA-DR phenotype of antigen-presenting cells.

Antigen-specific proliferation of human T cells sensitized in vitro was found to be macrophage dependent and HLA-DR restricted. Primary sensitization or secondary restimulation did not occur in the absence of antigen-presenting macrophages. The macrophage requirement for secondary restimulation was restricted by specificities shared between macrophages used for primary sensitization and T cells of the HLA-DR locus. Moreover, the magnitude of the response to antigen appeared to be related to the number of HLA-DR haplotypes shared between antigen-presenting cells in primary and secondary cultures. This observation could be attributed to a clonal response of the T cells with respect to HLA-DR on macrophages. Using HLA-DR 3/5 heterozygous KLH-primed T cells, elimination of cells responsive to antigen-pulsed HLA-DR 3/3 macrophages by thymidine suicide techniques left intact responsiveness to antigen-pulsed HLA-DR 5/5 macrophages. Tp determine whether the genetic restriction was dictated by the HLA-DR genotype of the responding lymphocytes or the HLA-DR phenotype of the responding lymphocytes or the HLA-DR phenotype of the antigen-pulsed macrophages, allogeneic macrophages were used to present antigen in primary culture. After elimination of alloreactive cells, proliferation in secondary cultures was found to be dependent on HLA-DR determinants shared between macrophages used for secondary restimulation and those used in primary sensitization, regardless of the HLA-DR genotype of the responding T lymphocytes.