Differential effect of anti-beta 2-microglobulin on IL 2 production and IL 2 receptor expression in the primary mixed lymphocyte culture reaction.
The mechanism of inhibition of the proliferative response in primary mixed lymphocyte culture (1 degree MLC) by antibodies to beta 2-microglobulin (beta 2m) was investigated. It is demonstrated that anti-beta 2m antibodies inhibit the production of interleukin 2 (IL 2). In contrast, the expression of IL 2 receptor is not affected by anti-beta 2m. The addition of purified exogenous IL 2 to the antibody-treated 1 degree MLC can completely restore the proliferative response, indicating that anti-beta 2m does not interfere with IL 2 binding to its receptor. Similarly, anti-beta 2m does not interfere with the capacity of IL 2-dependent T cell lines or T cell clones to respond to exogenous IL 2. The inhibition of cell proliferation and IL 2 production by anti-beta 2m is maximal when the antibody is added at the beginning of 1 degree MLC culture, and no effect of anti-beta 2m is seen when added after 3 days of culture. Anti-beta 2m has no effect on mitogen-induced cell proliferation and IL 2 production. Anti-beta 2m acts on the responder cell population, as demonstrated in experiments in which responder cells or stimulator cells are treated separately with the antibody. The expression of HLA-class II antigens (i.e., HLA-DR and DQ (DC) on the T cells activated on 1 degree MLC is not affected by anti-beta 2m. These studies indicate that the HLA-beta 2m class I antigen complex plays a role in T lymphocyte activation via release of IL 2, and suggest the existence of different mechanisms for activation of IL 2 producers and IL 2 responders in 1 degree MLC.
Chouaib
S
S
Welte
K
K
Dupont
B
B
D000911:Antibodies, Monoclonal / Q000502:physiology*; D001667:Binding, Competitive; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008223:Lymphoma / Q000276:immunology; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D001613:beta 2-Microglobulin