Allostimulatory analysis of a newly-defined and widely-distributed Mls superantigen

We previously noted that Mls^a,c C58/J responder cells proliferated unexpectedly to H-2^k-compatible Mls^a or Mls^c prototypic stimulator cells in a primary mixed lymphocyte reaction. The present investigation was performed to evaluate whether the response of C58/J T cells to these H-2- and Mls-compatible stimulator cells could functionally identify a newly-defined member of the Mls superantigen family through its allostimulatory ability. We observed that C58/J responder cells also proliferated when cultured with H-2-compatible prototypic Mls^null, Mls^b (nonstimulatory), or Mls^a,c splenic stimulator cells. The widely distributed nature of the non-MHC ligand recognized by C58/J T cells is indicated by the finding that 11 of 12 H-2^k inbred mouse strains clearly expressed this specificity. A gradient of stimulatory capacity from low to high across this newly-defined non-MHC difference was detected with splenocytes from these different inbred mouse strains. The Mls^a,c genetic composition of C58/J was confirmed by the observation that crossing C58/J with parental B10.BR (responsive to both Mls^a and Mls^c determinants) generated F₁ progeny that were unresponsive to H-2^k-compatible Mls^a, Mls^c, or Mls^a,c stimulator cells. Like prototypic Mls^a and Mls^c, the non-MHC specificity recognized by C58/J responder cells, termed Mls^f, was particularly sensitive to radiation (versus mitomycin C) treatment of the stimulator cells, was greatly augmented after anti-IgD activation of splenic stimulator cells, was blocked with anti-MHC class II antibody, and was effectively presented by phenotypically normal female but not B cell-defective xid⁺ male CBA/N F₁ stimulator cells.Address correspondence and offprint requests to: J. J. Ryan