Endogenous Ligands Selecting T Cells Expressing Particular Vβ Elements

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular Vβ segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple Vβ11 and Vβ3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the Vβ11/Vβ3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3' LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3' LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.