(BALB/c x C57BL/6)F1 mice are tolerant to undetectable mixed haplotype A beta dA alpha b and mixed isotype A beta dE alpha d self class II molecules.

The existence of mixed haplotype A beta dA alpha b and mixed isotype A beta dE alpha d molecules was demonstrated in A beta d gene introduced C57BL/6 (B6) transgenic and in A beta dE alpha d double gene introduced B6 transgenic mice, respectively. Using alloreactive and antigen reactive T-cell clones, these mixed class II molecules were shown to function as mixed lymphocyte culture reaction (MLR) stimulating determinants and restriction elements for antigen recognition by T cells. The amounts of expression of these mixed class II molecules were sufficient for the stimulation of alloreactive T cells in primary MLR culture. (BALB/c x B6)F1 (CBF1) mice were shown not to express functional mixed haplotype and mixed isotype class II molecules using alloreactive and antigen reactive T-cell clones. Interestingly, however, CBF1 mice did not respond to such mixed haplotype and mixed isotype class II molecules. These results show that CBF1 mice do not respond to undetectably-expressed class II molecule and suggest that they are tolerant to undetectable self class II molecules. The possible interpretations for this are discussed.