R24 anti-GD3 ganglioside antibody can induce costimulation and prevent the induction of alloantigen-specific T cell clonal anergy.
R24 is a monoclonal antibody directed against the cell surface ganglioside GD3. It can detect GD3 on the surface of a subset of T lymphocytes and can stimulate proliferation and secretion of cytokines in vitro. In the present report, we examined the effects of the R24 antibody upon antigen-specific T cell response, employing an HLA-DR7-specific T cell clonal model. As previously shown, primary stimulation of HLA-DR7-specific alloreactive T cell clones by transfectants expressing HLA-DR7 alone (t-DR7) in the absence of B7 co-stimulation resulted in anergy. Binding of cell surface GD3 on HLA-DR7-specific alloreactive T cell clones with R24 under these anergizing conditions resulted in interleukin-2 (IL-2) accumulation and prevented the induction of alloantigen-specific T cell clonal anergy. Binding of GD3 by R24 also prevented anergy under conditions where B7:CD28 interactions were blocked by CTLA4-Ig. The effect of R24 was abrogated in the presence of a combination of monoclonal antibodies for the alpha and beta chains of the IL-2 receptor (IL-2R) or a neutralizing anti-IL-2 antibody. R24 does not appear to interact directly with the IL-2R since incubation of T cell clones with R24 did not induce early activation of IL-2R associated Jak kinases, Jak1 and Jak3, as was induced following incubation with IL-2. In contrast, incubation of HLA-DR7-specific clones with t-DR7 in the presence of R24 did result in phosphorylation of IL-2R related Jak kinases after 24 h. Our data indicate that the membrane ganglioside GD3 structure recognized by R24 may play an important role in antigen-specific T cell clonal response.
Boussiotis
V A
VA
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Pardo
N A
NA
Collins
H
H
Houghton
A
A
Ritz
J
J
Nadler
L M
LM
Soiffer
R J
RJ
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002999:Clone Cells; D005732:Gangliosides / Q000502:physiology*; D015809:HLA-DR7 Antigen / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000502:physiology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D015809:HLA-DR7 Antigen; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C026226:ganglioside, GD3