Abstract
P3 is a murine IgM mAb that recognize N-glycosylated gangliosides, sulfatides, and antigens expressed in melanoma, breast, and lung human tumors. This antibody has the ability to trigger an IgG antibody response in the syngeneic BALB/c model, even when it is administered in the absence of adjuvant or carrier protein. The mechanism by which the P3 mAb, a self-immunoglobulin, induce this immune response in the absence of co-stimulatory or classical danger signals is still unknown. In the present paper we show that the high immunogenicity of P3 mAb depends not only on CD4 but also on CD8+ T cells, since the depletion of CD8+ or CD4+ T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8+ T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8+ T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4+ and CD8+ T cells. These results show new possibilities for B and CD8+ T cells interactions during the immune response elicited by a self-protein. Furthermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.
Highlights
P3 mAb is an Ab1 antibody that recognizes NeuGc-containing gangliosides, sulfated glycolipids, and antigens present in different human tumors including those from the lung, breast, and melanoma (Vazquez et al, 1995)
For this purpose we evaluated the IgG antibody response induced in BALB/c mice immunized subcutaneously with P3 only in phosphate buffered saline (PBS) or emulsified in Freund’s adjuvant
These mice received only one dose of P3 mAb, the anti-P3 antibody response continued increasing in time and 49 days after immunization reached levels that did not show significant differences with those obtained in the animals immunized with four doses
Summary
P3 mAb is an Ab1 antibody that recognizes NeuGc-containing gangliosides, sulfated glycolipids, and antigens present in different human tumors including those from the lung, breast, and melanoma (Vazquez et al, 1995). VH P3 is of germ line origin and belongs to the Q52 (VH II) gene family, previously observed in autoantibodies against gangliosides and frequently used by CD5+ B lymphocytes (Perez et al, 2001) This antibody is capable of triggering a strong anti-idiotypic (Ab2) response in the syngeneic model, even in the absence of adjuvant or carrier protein (Vazquez et al, 1998), which is a phenomenon rarely observed (Baskin et al, 1990; Maruyama et al, 2002). Reitan and Hannestad (2001) analyzed the syngeneic immunogenicity, in the absence of adjuvant, of the idiotypes of 73 mAb of IgM isotype These researchers reported that the four antibodies that generated high levels of anti-idiotypic IgG antibodies, were coded by germ line genes
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