Structural heterogeneity of the human Ia molecular pool as detected by cross-reacting mouse monoclonal antibodies.

Three monoclonal antibodies (Mab), H39.49.5, H40.242.3, and H40.164.3, produced in an A.TH anti-A.TL system and reacting with determinants expressed either on I-Ak, on I-Ek, or on I-Ak and I-Ek molecules, respectively, have been used to analyze, at the structural level, the molecules of the human Ia pool against which they cross-react. The results indicate that the human Ia pool can be dissected out by the use of the A.TH anti-A.TL Mab in distinct families, which display structural variations not only among each other but also with respect to the previously defined NG1 and NG2 Ia subsets. In two distinct Ia pools analyzed (from Raji cells: HLA-DR 3,W6, and from LG-2 cells: HLA DR 1,1), the three A.TH anti-A.TL cross-reacting antibodies recognized molecules in which the allelic polymorphism was confined to the beta subunits. Moreover, within the same Ia pool, the alpha subunits as well as the beta subunits were shown to be different from each other. These results are discussed in the context of the present knowledge of the heterogeneity of the human Ia pool and of the possible similarity between gene products of the mouse H-2-I region and the human HLA-D counterpart.