Delineation of serologically distinct monomorphic determinants of human MHC class II antigens: evidence of heterogeneity in their topographical distribution.

Three monoclonal antibodies (mAbs), FMC4, FMC14 and FMC15, which react with invariant sites of major histocompatibility complex (MHC) class II (Ia-like) molecules were studied in various serological assays. Sequential immunodepletion experiments show that all three epitopes are present on the same class II molecules. However, a minor subset may exist which does not express epitope 15. In competitive binding assays, using several different B-lymphoblastoid cell lines (B-LCLs), e.g. BRISTOL-8 8392, B-85, RAJI, 8866, CESS-B and LD-B, FMC4 did not block the binding of FMC14, or FMC15, and vice versa. In contrast, mutual inhibition was observed between FMC14 and FMC15. Furthermore, pairwise combinations of saturating amounts of FMC4 + FMC14 and FMC4 + FMC15 gave additive binding whilst FMC14 + FMC15 did not. These results demonstrate that epitopes 4 and 14/15 are spatially distinct; 14 and 15 on the other hand appear to be spatially related. However, contrary to this partial and reciprocal inhibition was consistently observed between FMC4 and FMC14 on two other LCLs, namely DAUDI and BALM-2. Furthermore, on certain cells, FMC14 and FMC15 show markedly disparate binding. Taken together, these observations indicate that the juxtaposition of certain epitopes on class II antigens can vary according to the cell type. This demonstrates a hitherto unreported heterogeneity of antigenic determinants and of their topographical distribution on the class II molecule.