We characterized autoreactive T-cell clones derived from (NZB x NZW)F1 (B/WF1) mice. These autoreactive T-cell clones are shown to be CD4+ by immunofluorescence staining and to belong to Th2 type by cytokine release assay. Specificity analysis revealed the existence of mixed haplotype A beta z/A alpha d major histocompatibility complex (MHC) class II molecule-specific T-cell clones as well as A beta z/A alpha z- or A beta d/A alpha d-specific T-cell clones. Some but not all of the mixed haplotype A beta z/A alpha d-specific autoreactive T-cell clones showed strong activity to induce IgG anti-DNA antibody production upon transfer to young (4-month-old) B/WF1 mice, indicating that T cells with these specificities might be involved in B/WF1 autoimmunity.