Unidirectional Responses to Mls Determinants in Vivo

Abstract

Polyclonal anti-Mls responses of peripheral (mature) and thymic (immature) lymphocytes were studied in vivo in terms of local host-versus-graft and graft-versus-host reactions. The level of stimulatory activity differed between the various types of Mls antigens, with Mlsa and Mlsd having the highest levels. Mlsc a lower level, and Mlsb the lowest level. The immunogenicity of Mlsa and Mlsd may not be identical, since Mlsd mice responded to the Mlsa determinant, while Mlsa mice did not react with the Mlsd determinants. This suggests that the anti-Mls response is unidirectional. The fact that Mlsb mice made tolerant at birth to Mlsd (Mlsa) antigens behave like Mlsd (Mlsa) mice when responding to Mls antigens supports this suggestion. Furthermore, thymus cells from the Mlsa-tolerized BALB/c (Mlsb) mice were unresponsive to both Mlsa and Mlsd antigens, while those made tolerant to Mlsd were responsive to Mlsa. These results indicate that the polyclonal response to the strongly immunogenic Mlsa,d antigens is unidirectional, and that the immunogenicity of Mlsa and Mlsd is not identical. Based on the results of tolerance experiments and data on T-cell clones, we suggest that the difference in immunogenicity between Mlsa,b,d antigens is due to different efficiencies of the responding T-cell populations, probably because of a quantitative difference in a single common antigenic determinant expressed in each Mls haplotype, which results in different levels of stimulation of T cells according to the avidity for the determinant.