DISSOCIATION AND EXCHANGE OF THE BETA-2-MICROGLOBULIN SUBUNIT OF HLA-A AND HLA-B ANTIGENS

Human histocompatibility antigens HLA-A, HLA-B, and HLA-C are a complex of two noncovalently associated subunits: a heavy chain glycoprotein (α) carrying the genetic polymorphism and an invariant light chain β2-microglobulin (β2m). Upon incubation of papain-solubilized HLA with radiolabeled urinary β2m, the latter is incorporated into HLA, where it substitutes for the preexisting β2m that has dissociated from the complex. The association-dissociation equilibrium that governs this β2m exchange reaction was investigated and found to be characterized by a long lifetime of the complex (half-life of 80 min at 37°C) and a relatively low K(d)(4nM). The β2m exchange was used as the basis of a radioimmunoassay for HLA antigens with radiolabeled β2m as a unique label for all HLA specificities. In a similar fashion, radiolabeled β2m can be incorporated into HLA at the cell surface. Although the process is slower and less extensive than in solution, it can be used as a means to tag cells with specific probes for HLA antigens.