Cell-mediated lympholysis (CML) was studied in a family containing two siblings in whom genetic recombination had occurred in the HLA complex. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus.

Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D.

HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis.

In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.

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