The use of transfected fibroblasts and transgenic mice establishes that stimulation of T cells by the Mycoplasma arthritidis mitogen is mediated by E(α)

Mycoplasma arthritidis produces a soluble protein which is active for murine and human lymphocytes when presented by Ia-bearing accessory cells. By using fibroblasts transfected in vitro with various class II Ag, we demonstrated that presentation of the M. arthritidis mitogen [MAM] to T cells was mediated by E(α)-containing molecules. We also showed that splenocytes from transgenic mice expressing E(α) heterozygously (B10.TRG E(α)⁺) or homozygously (B10.E(α)TG+/+) underwent a similar proliferation in response to MAM as compared with the failure of control B10.TRG E(α)^- splenocytes to respond to MAM. Although splenocytes from inbred C3H and CBA mice exhibited much higher proliferative responses to MAM than did those from B10.TRG.E(α)⁺ or B10.E(α)TG+/+ mice, flow cytometry showed similar levels of E(α) expression. Furthermore, γ-irradiated splenocytes from B10.TRG E(α)⁺ mice presented MAM to T hybridoma cells with a similar efficacy as did splenocytes from C3H mice. The lesser response to MAM of lymphocytes from the E(α) transgenic mice as compared with those from C3H and B10.K mice was likewise not due to differential expression of their V(β) TCR. We conclude that presentation of MAM to T cells is accomplished by E(α)-containing molecules. The studies also suggest that the conserved, nonpolymorphic regions of class II molecules may play an important role in host immune response to microbial products.