A glycophospholipid anchor is required for Qa-2-mediated T cell activation.
A number of lymphocyte surface proteins are anchored in the cell membrane by glycophosphatidyl inositol (known as GPI) linkages instead of hydrophobic protein domains. Treatment of mouse T lymphocytes with antibodies specific for two such proteins, Thy-1 and Ly-6, are known to induce proliferation. We have found that antibodies specific for Qa-2, a GPI-anchored class I histocompatibility antigen, can also activate mouse T cells. To determine whether the GPI-anchor is important for this pathway of cell activation, we produced transgenic mice expressing either normal GPI-anchored Qa-2, or Qa-2 molecules with a membrane-spanning protein domain derived from H-2. Our studies show that only lymphocytes from transgenic mice carrying GPI-anchored forms of Qa-2 can be activated in vitro by Qa-2-specific antibodies. We also show that transgenic mouse T cells expressing a GPI-anchored form of H-2Db can be activated by anti-H-2Db antibodies. These results strongly indicate that the GPI-anchor is critical for this pathway of T cell activation.
Robinson
P J
PJ
Transplantation Biology Section, Clinical Research Centre, Harrow, Middlesex, UK.
Millrain
M
M
Antoniou
J
J
Simpson
E
E
Mellor
A L
AL
D000818:Animals; D000906:Antibodies / Q000276:immunology; D003001:Cloning, Molecular; D004261:DNA Replication; D005796:Genes; D006017:Glycolipids / Q000276:immunology*; D017261:Glycosylphosphatidylinositols; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010716:Phosphatidylinositols / Q000276:immunology*; D015183:Restriction Mapping; D013045:Species Specificity; D013601:T-Lymphocytes
D000906:Antibodies; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010716:Phosphatidylinositols; C032907:Q surface antigens