One-way positive cellular reactions between two HLA-A, B, C, D/DR genotypically identical brothers following active...

The HLA-D/Dr region in man encodes major determinants which stimulate T lymphocytes to proliferation. The genetic organization of this region is apparently complex and is at present largely unknown. One obstacle is the scarcity and quality of available typing reagents. In an attempt to obtain high quality anti-DR sera, a series of active immunizations was performed between highly selected, healthy unrelated donors and recipients. One recipient (AR8) was immunized using cells incompatible for HLA-A2, B40 (w60), Cw3 and D/DRw6 and readily developed anti-A2 and B40 antibodies but no anti-C, CR, or other antibodies. When tested against his HLA genotypically fully identical brother using te cellular MLC, PLT, or CML techniques before immunization, results were mutually negative as expected. Following immunization, however, AR8 was able to mount MLC, PLT, and possibly CML responses against lymphocytes from the brother while the reverse combinations remained negative. When tested in the family the trait(s) thus identified seems to be maternally inherited. These results suggest the existence of minor histocompatibility determinants encoded from regions not closely linked to HLA. The brother of AR8 and the immunizing donor thus seem to share one or more determinants not possessed by AR8.