Anti-self receptors. I. Direct detection of H-2L region-restricted receptors on murine thymocytes.

Abstract

A high proportion (20--50%) of murine thymocytes form rosettes with either syngeneic or allogeneic erythrocytes. The specificity of this interaction was investigated by measuring the ability of different erythrocyte sonicates to inhibit rosette formation. With erythrocyte sonicates from recombinant mouse strains it was demonstrated that rosetting with syngeneic erythrocytes was mediated by H-2L and/or H-2D region-restricted receptors. The specificity of autorosetting was directly mapped to the H-2L region by the inability of erythrocyte sonicates from the BALB/c-H-2dm2 mutant, an H-2L-deletion mutant, to inhibit the rosetting of wild-type (BALB/c) thymocytes. The B10,2D2-H-2dm1 mutant, which has substantially modified H-2L and H-2D antigens, supported this conclusion. Furthermore, anti-H-2L sera were able to specifically block the inhibition of rosetting by erythrocyte sonicates. The above procedures clearly implicated the H-2L region in the thymocyte rosetting of d and k haplotypes. With the s haplotype the rosetting receptor was mapped to the H-2L/H-2D region, whereas with the b and q haplotypes rosetting was only mapped to the D end of the H-2 complex. This study also suggested complete cross-reaction between the thymocyte receptors carried by the k and d haplotypes, whereas the receptors of b, q, and s haplotypes were haplotype specific. In addition, the inhibition assay indicated that the rosetting of thymocytes with allogeneic and xenogeneic (rat) erythrocytes was mediated by a receptor primarily directed against self-H-2L. Finally, the critical role played by the H-2L region in this rosetting phenomenon was demonstrated by the inability of thymocytes from the H-2L-deletion mutant (H-2dm2) to rosette with syngeneic, allogeneic (rat) erythrocytes.