Xid-defective male (CBA/N X C57BL/6)F1 accessory cells present bovine insulin to long-term cultured F1-restricted T-cells.

The reactivity of H-2b-restricted murine T cells towards bovine insulin was reported to depend on the expression of Ia. W39, a private specificity of I-Ab, on antigen-presenting cells. Cells of male (CBA/N X B6)F1 mice carrying the mutation xid on the X chromosome lack IA. W39 on the cell surface. These cells are unable to present bovine insulin to primed T cells derived from female (CBA/N X B6)F1 mice. We show here that spleen cells of male (CBA/N X B6)F1 hybrids served perfectly as accessory cells for the insulin-dependent induction of a proliferative response of long-term cultured T cells with (B10 X B10.BR)F1 genotype, restricted to recognizing insulin in the context of F1-unique I-A determinants.l The epitope on the insulin molecule essential for stimulation was determined to depend on the glutamic acid residue in position 4 of the A chain of insulin. This contracts with the H-2b-restricted response of B6 mice to bovine insulin, which appears to be directed at the A chain loop determinant (amino acids A8 and A10). These data suggest that distinct I-Ab-encoded structures, the expression of which is regulated independently, may serve as components of restriction elements for H-2b and (H-2b X H-2k)F1 restricted T cells, which are specific for different epitopes of bovine insulin.