Helper cells activated by allogeneic H-2K or H-2D differences have a Ly phenotype distinct from those responsive to I differences.

Helper activity for the primary in vitro response to sheep erythrocytes was induced by recognition of foreign major histocompatibility antigens. The Lyt phenotypes of helper activity induced by differences in the whole haplotype, K or D antigens, I region antigen, or by differences at the M1s locus were determined. All allohelper cells expressed Ly1. In a single spleen cell suspension helper activity generated in response to the whole haplotype, I region, or M1s antigens was derived from an Ly2-negative population, whereas helper activity generated to K or D alone was derived from a population of Ly2-positive cells. Mixtures of anti-Ly1 and anti-Ly2 treated populations were unable to generate helper activity in response to K or D differences. Such helper activity was therefore dependent on the presence of Ly12 cells. It was concluded that the Ly phenotype of the helper cells is not determined solely by the T cell function but is influenced by the region of the major histocompatibility complex that is recognized. Possible interpretations of these findings are discussed.