Related Experiment Videos
Endogenous ligands selecting T cells expressing particular V beta elements
K Tomonari1, S Fairchild, O A Rosenwasser
1Transplantation Biology Section, MRC Clinical Research Centre, Harrow, Middlesex, U.K.
Abstract:
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 V beta segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple V beta 11 and V beta 3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the V beta 11/V beta 3 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.
Insights
Mouse mammary tumor virus (MMTV) encodes endogenous ligands, known as minor lymphocyte stimulatory antigens (Mls), which delete specific T cells. These Mls act as superantigens, with the MMTV 3' LTR encoding a type II membrane glycoprotein responsible for this function.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands induce T cell deletion.
- Mouse mammary tumor virus (MMTV) has been identified as the source of these Mls and T cell-deleting ligands.
- These ligands share characteristics with bacterial superantigens, binding MHC class II and TCR.
Purpose of the Study:
- To review genetic analyses of V beta 11 and V beta 3 deletion ligands.
- To demonstrate MMTV's role in encoding these ligands.
- To investigate the molecular basis of MMTV-encoded superantigen function.
Main Methods:
- Genetic analyses of V beta 11 and V beta 3 deletion ligands.
- In vitro translation of the MMTV 3' LTR open reading frame (ORF).
Main Results:
- MMTV is involved in all analyzed V beta 11 and V beta 3 deletion ligands.
- The 3' LTR of the MMTV genome encodes superantigen function.
- In vitro translation identified a type II integral membrane glycoprotein as the major product of the 3' LTR ORF.
Conclusions:
- MMTV-encoded type II membrane glycoproteins function as superantigens, analogous to bacterial superantigens.
- These glycoproteins interact with MHC class II and TCR distinct from conventional peptide antigens.
- Further research is needed to understand the mechanisms of T cell deletion and Mls transfer.