The mutant lpr gene causes a generalized massive T cell proliferation and an associated autoimmune disease in mice. The lpr T cells bear unusual membrane phenotypes and play a causative role in the pathogenesis of autoimmune disease through excess production of some lymphokines. Therefore, the "aberrant" T cells in lpr mice may be normal regulatory T cells in non-lpr-bearing mice, if nonproliferative. We thus attempted to produce a xenogeneic monoclonal antibody (ALP-1) directed against the lpr T cells. The ALP-1 monoclonal antibody reacted with the antigen Lp-1 distributing on about one half of the proliferating lymph node cells from MRL/Mp-lpr/lpr mice but not on the cells from non-lpr-bearing mice. Nevertheless, a significant number of Lp-1+ cells appeared in the lymph node and spleen cells from these normal mice after in vitro stimulation with mitogens. Functional studies revealed that either the treatment with ALP-1 plus complement of the antigen-primed splenic T cells from non-lpr-bearing mice or the addition of ALP-1 alone all but completely abolished the development of plaque-forming cells against sheep red blood cells in T-B cell coculture. Pretreatment of spleen cells with ALP-1 plus complement, however, did not affect other in vitro T cell functions such as mitogen-induced proliferative responses, interleukin 2 production, response in mixed lymphocyte culture (MLC) and the MLC-induced cytotoxic T cell activities. Thus, Lp-1+ T cells in normal mice are unique T cells that may play an important regulatory role in humoral immune response.