An exogenous mouse mammary tumor virus with properties of Mls-1a (Mtv-7).
The classical minor lymphocyte stimulating (Mls) antigens, which induce a strong primary T cell response in vitro, are closely linked to endogenous copies of mouse mammary tumor viruses (MMTV). Expression of Mls genes leads to clonal deletion of T cell subsets expressing specific T cell receptor (TCR) V beta chains. We describe the isolation and characterization of a new exogenous (infectious) MMTV with biological properties similar to the Mls antigen Mls-1a. In vivo administration of either Mls-1a-expressing B cells or the infectious MMTV (SW) led to an increase of T cells expressing V beta 6 followed by their deletion. Surprisingly, different kinetics of deletion were observed with the exogenous virus depending upon the route of infection. Infection through the mucosa led to a slow deletion of V beta 6+ T cells, whereas deletion was rapid after subcutaneous infection. Sequence analysis of the open reading frames in the 3' long terminal repeat of both this exogenous MMTV (SW) and of Mtv-7 (which is closely linked to Mls-1a) revealed striking similarities, particularly in the COOH terminus, which has been implicated in TCR V beta recognition. The identification of an infectious MMTV with the properties of a strong Mls antigen provides a new, powerful tool to study immunity and tolerance in vivo.
Held
W
W
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Shakhov
A N
AN
Waanders
G
G
Scarpellino
L
L
Luethy
R
R
Kraehenbuhl
J P
JP
MacDonald
H R
HR
Acha-Orbea
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D005814:Genes, Viral; D008198:Lymph Nodes / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008892:Milk / Q000382:microbiology; D016747:Minor Lymphocyte Stimulatory Antigens / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D016747:Minor Lymphocyte Stimulatory Antigens; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell