Interferon (IFN) beta-1b has been shown to alter the course of multiple sclerosis and to inhibit MHC class II expression, but its effect on antigen presentation has not been examined in a functional assay (Neurology 43 (1993) 655-661). The effect of IFN beta-1b on alloantigen presentation by human antigen-presenting cells (APC) including human fetal astrocytes (HFA) and microglia was examined. The effect of IFN beta-1b on the ability of B cells to present tetanus toxoid (TT) to TT-specific T cell lines was also examined. APC were pre-treated with IFN gamma (100 units/ml), IFN beta-1b (10-2000 units/ml), or a combination of IFN gamma and IFN beta-1b for 3 days and washed thoroughly prior to culture with allogeneic peripheral blood lymphocytes (PBL) for a period of 6 days. Lymphocyte proliferation was then measured by tritiated thymidine uptake. Treatment of the APC with IFN beta-1b resulted in a reduction in the IFN gamma-enhanced alloantigen-induced T cell responses. This reduction ranged between 50 and 70%, was associated with a 30-50% reduction in HLA class II (DR) and 35-40% reduction in ICAM-1 expression on the HFA used as APC. IFN beta-1b pretreatment of B cells reduced their constitutive and IFN gamma enhanced capacity to present TT to TT-specific T cell lines by 50-80%. This was associated with a 30 +/- 11% mean reduction in class II (DR) expression and approximately 50 +/- 1% reduction in ICAM-1 expression in IFN beta-1b + IFN gamma-treated B cells compared to IFN gamma-treated B cells (mean of three experiments).(ABSTRACT TRUNCATED AT 250 WORDS)