B-CD8⁺T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

Abstract

P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo. Interestingly, transfer of both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion of IFN-γ and IL-4, although this activation was not detected ex vivo. Interestingly, naïve CD8+ T cells increased the expression of activation markers and IFN-γ secretion in the presence of B-1a cells isolated from P3 mAb-immunized mice, even without in vitro restimulation. In contrast, B-2 cells were able to stimulate CD8+ T cells only if P3 was added in vitro. Using bioinformatics, a MHC class I-binding peptide from P3 VH region was identified. P3 mAb was able to induce a specific CTL response in vivo against cells presenting this peptide. Both humoral and CTL anti-idiotypic responses could be mechanisms to protect against the self-reactive antibody, contributing to keeping the tolerance to self-antigens.

Monoclonal Antibody chP3R99 Reduces Subendothelial Retention of Atherogenic Lipoproteins in Insulin‐Resistant Rats: Acute Treatment Versus Long‐Term Protection as an Idiotypic Vaccine for Atherosclerosis

“…The chP3R99 has been developed to recognize sulfated glycosaminoglycans found within the chondroitin sulfate family of proteoglycans. 37 , 38 , 39 , 56 , 57 In addition to antigen recognition mediated by the CDR motifs of the P3 idiotype, the region contains both CD4 + and CD8 + T‐cells epitopes, conferring a high immunogenicity that is preserved within the chP3R99 mAb. The idiotope is a generic “structural” term given to a unique sequence of antigenic determinants (epitopes) located on the variable portion of any given antibody.…”

Monoclonal antibody chP3R99 reduces subendothelial retention of atherogenic lipoproteins in Insulin-Resistant rats:Acute treatment versus long-term protection as an idiotypic vaccine for atherosclerosis

“…The chP3R99 has been developed to recognize sulfated GAGs found within the chondroitin sulfate family of proteoglycans (37–39, 56, 57). In addition to antigen recognition mediated by the complementarity-determining region (CDR) motifs of the P3 idiotype, the region contains both CD4 + and CD8 + T-cells epitopes, conferring a high immunogenicity which is preserved within the chP3R99 mAb.…”