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Murine marrow coexpressing H2-Dsp2 and H2-Db on host natural killer cell rejection
1Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Background:
Class I molecules may inhibit or activate natural killer (NK) cells. H2-Dd, -Ld, or -Dsp2 (the latter derived from spretus mice) on bone marrow cells (BMC) are recognized and rejected by NK1.1+ NK cells. BMC of intra-H2 recombinants between H2sp2 and H2b were analyzed. The 9347 and R40 KbIbBat2b/Tnf(sp2)Dsp2 BMC were rejected by B6 hosts. However, B6 hosts reject and accept KbDsp2Db R40 x B6 and 9347 x B6 BMC, respectively. Thus, Db and/or H2-Bat2/Tnf interval genes may regulate the immunogenicity of H2-Dsp2+ BMC.
Methods:
R40 or 9347 mice were crossed with DBA.Db (H2d, Db) transgenic mice to produce F1 and F2 progeny. DNA synthesis (proliferation) in host spleens was the measure of marrow graft success. Results. (1) BMC of H2(9347 or R40)+ H2d-Db+ (but not Db-) F2 progeny grew in B6 hosts. (2) BMC of H2(9347 or R40) x DBA.Db F1 Kb/dDsp2/dDb progeny were rejected by B6, but not by B6D2F1 (H2b/d) or D8 (H2b, Dd) hosts. (3) NK cells were the effectors.
Conclusions:
Db can reduce the immunogenicity of Dsp2+ BMC (F2 data), but not of Dd+ BMC (F1 data). Growth of F2 H2(R40) Db+, but not F1 R40 x B6, BMC grafts in B6 hosts could be based on gene(s) differences in the H2-Bat2/Tnf region. Alternatively, non-H2 genes of DBA/2 might be involved. The genes would provide peptides for Db heavy chains to form "protective motifs" that send negative signals to host NK cells.