Biochemical analysis of the mouse mammary tumor virus long terminal repeat product. Evidence for the molecular structure of an endogenous superantigen.
Recent reports have shown that both exogenous and endogenous mouse mammary tumor viruses (MMTV) can encode superantigens. Transfection and transgenic studies have identified the open reading frame (ORF) present in the 3' long terminal repeat (LTR) as encoding superantigen function. In this study, we have used an in vitro translation system in an attempt to characterize the molecular nature of the protein encoded by the 3' ORF of Mtv-8. Using various constructs encoding full-length and truncated versions of the ORF product, we report that the hydrophobic region close to the amino terminus of the 36-kDa protein can function as a transmembrane domain. Protease digestion experiments also demonstrate that the protein has a type-II transmembrane conformation with an extra-cytoplasmic carboxy terminus. Since this hydrophobic region is conserved between all known MMTV, we speculate that LTR ORF, including those proposed to encode the minor lymphocyte stimulatory antigens, are also capable of encoding type-II transmembrane glycoproteins. The polymorphism between MMTV LTR ORF products, which correlates with deletion phenotypes, is predominantly in the carboxy-terminal extracellular region, consistent with a major role in interaction with the T cell receptor.
Knight
A M
AM
Transplantation Biology Section, Clinical Research Centre, Harrow Middlesex, Great Britain.
Harrison
G B
GB
Pease
R J
RJ
Robinson
P J
PJ
Dyson
P J
PJ
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D012091:Repetitive Sequences, Nucleic Acid
D000956:Antigens, Viral