Species cross-reactive Ia determinants: detection with a monoclonal antibody to human Ia of a murine Ia. 7 epitope.

A.TH anti-A.TL alloserum has previously been shown to react with monomorphic determinants of human Ia molecules. In an attempt to produce monoclonal antibodies detecting human-mouse cross-reacting epitopes, A.TH mice (Is) which lack I-E antigens were immunized with human Ia glycoproteins. Five hybridoma lines were established which recognize monomorphic human Ia determinants. Only one of the lines, 21w4, is reactive with murine cells and also with pig and sheep cells but not with rat cells. Binding studies to murine target cells show a strain distribution analogous to that of an Ia. 7-like specificity. The binding of 21w4 antibody to human and murine cells was compared to that of two other monoclonal antibodies directed to the murine Ia. 7-like specificity. Although all three antibodies had a similar pattern of reactivity with cells of different mouse strains, only 21w4 bound to the human cells tested. Competitive inhibition studies on murine cells have revealed that the epitopes were spatially related but not identical. Our results support the view that Ia. 7, the putative species cross-reacting specificity, might be composed of clusters of epitopes with variable degrees of conservation throughout evolution.