MHC class II A(α) and E(α) molecules determine the clonal deletion of V(β)6⁺ T cells. Studies with recombinant and transgenic mice

Interactions between MHC class II genes and minor lymphocyte stimulating (Mls) associated products are responsible for clonally deleting self-reactive T cells in mice. Here we demonstrate the role of the intact I-A and I-E molecules as well as the individual A(α) chains in the deletion of cells bearing the V(β)6 TCR. DBA/1 (H-2(q), Mls-1^a) mice were crossed with various inbred congenic, recombinant, and transgenic strains and the F₁'s were screened for V(β)6 expression. All I-E⁺ strains were fully permissive in deleting V(β)6⁺ T cells. I-E^- strains expressing I-A(b.f.s.k.p.) permitted only partial deletion, while I-A(q) strains showed no deletion. Recombinant I-A(q) and I-A(f) strains which expressed E(α)(k) chain in the absence of E(β) chain showed a decrease in V(β)6⁺ T cells as compared to their H-2(q) and H-2(f) counterparts. Furthermore, transgenic mice expressing E(α)(k) A(β)(q) gene in an H-2(q) haplotype (E(α)(k) A(β)(q)?) gave similar results to that of the recombinants in deleting V(β)6 T-cells. The role of the I-A molecule was also shown by the partial deletion of V(β)6⁺ T cells in H-2(q) mice expressing transgenic I-A(k) molecules. These results demonstrate that the E(α) chain is important in the deletion of V(β)6 T-cells in Mls-1a mice. The role of A(α) chain is also implied by the permissiveness of E(α)(k) A(β)(q) but not A(α)(q) A(β)(q) molecules in the deletion of V(β)6⁺ T cells.