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R24 anti‐GD3 ganglioside antibody can induce co‐stimulation and prevent the induction of alloantigen‐specific T cell clonal anergy
Author(s) -
Boussiotis Vassiliki A.,
Pardo Nichole A.,
Collins Heather,
Houghton Alan,
Ritz Jerome,
Nadler Lee M.,
Soiffer Robert J.
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830260928
Subject(s) - biology , monoclonal antibody , t cell , interleukin 2 , antibody , microbiology and biotechnology , immunology , stimulation , cytokine , immune system , endocrinology
Abstract 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 α and β 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.