Identification of a membrane antigen that is distinct from the interleukin 2 receptor and that may be required for interleukin 2-driven proliferative responses.
During the course of studies designed to raise murine monoclonal antibodies to a guinea pig alloreactive T cell line, an IgM monoclonal antibody (5C3) was identified that completely inhibited the alloantigen and IL 2-dependent proliferative response of the immunizing colony and other alloreactive T cell colonies with different antigen specificities. Tissue distribution on the FACS demonstrated that the surface antigen defined by 5C3 was preferentially expressed on T cells activated by mitogen, alloantigen, or antigen. 5C3 was also a potent inhibitor of alloantigen- and antigen-induced T cell proliferation. In addition, 5C3 substantially inhibited the proliferative response of guinea pig Con A-induced blast cells to guinea pig IL 2-containing culture fluids and to a preparation of partially purified human IL 2 but was a poor inhibitor of mitogen-induced T cell proliferation. Blast cells obtained from the co-culture of mesenteric lymph node cells with Con A in the presence of 5C3 lacked the surface molecule defined by 5C3. The 5C3- and 5C3+ blast populations, nevertheless, absorbed equivalent amounts of IL 2, which suggested that 5C3- blasts were not deficient in the expression of IL 2 receptors. However, 5C3- blast cells failed to proliferate in response to IL 2-containing culture fluids. Furthermore, 5C3 had no inhibitory activity on either the binding or subsequent degradation of radiolabeled human IL 2 by guinea pig IL 2 receptors. These data suggest that 5C3 recognizes a component of a putative IL 2 receptor-effector complex distinct from the IL 2 receptor and that this molecule plays a critical role in the processing or generation of the growth signal IL 2 transmits to T lymphocytes.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis*; D002469:Cell Separation; D000939:Epitopes; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2