Ia-positive stimulator cells are required in primary, but not in secondary, mixed leukocyte reactions against H-2K...

The expression of I region gene products on stimulator cells in primary and secondary MLR directed against differences determined by the K or D regions of the H-2 gene complex was examined in B10-congenic mice. Treatment of the stimulator cells with anti-Ia antisera and complement (C) eliminates stimulation in primary MLR against K or D region gene products, indicating that the stimulator cells must express Ia antigens on their membranes. Further, stimulation in primary MLR against D region antigens is abolished by treatment of the stimulator cells with C and antisera against either I-A or I-E subregion products, but not by treatment of stimulator cells with C and antisera against I-J subregion products. Therefore, these stimulator cells express on their membranes both I-A and I-E subregion gene products, but not I-J subregion gene products. In contrast, in secondary MLR against K or D region gene products, treatment of stimulator cells with anti-Ia antisera and C does not abolish stimulation, indicating that Ia-negative cells can stimulate primed responder cells. These results indicate that the mechanisms of cell-cell recognition necessary in secondary MLR against K or D region gene products are different from those in primary MLR to the same products.