A human B cell line, ARH, was transfected with a murine major histocompatibility complex class II gene (I-A(k)). One of the transfectants, ARH5.5, which strongly expresses I-A(k) molecules was found to be capable of presenting soluble antigens to I-A(k)-restricted, antigen-specific murine helper T cell (Th) clones. When ARH5.5 was treated with either chloroquine or paraformaldehyde prior to the antigen pulse, it failed to present a protein antigen, ovalbumin, but retained the ability to present a peptide, indicating that the presentation was dependent on processing. The xenogeneic interaction of co-stimulatory molecules on the human antigen presenting cell (APC) and the murine Th cell was assessed by using antibodies against adhesion molecules. We found that the xenogeneic interaction of LFA-1/ICAM-1 acted as a strong co-stimulator of the antigen presentation by ARH5.5, while that of CD2/LFA-3 had only little stimulatory effect. These results suggest that the interaction between some of the adhesion molecules on APC and Th can cross the species barrier. The experimental system presented here is simple and useful for analyzing human APC function, separately from T cell function, especially when the dysfunction of APC associated with viral infection with human tropism is considered.