T cell activation by anti‐idiotypic antibody: mechanism of interaction with antigen‐reactive T cells

Abstract

It has been shown that the activation of T cells by an anti-idiotypic antibody (anti-Id) TB71 containing an internal image of the corresponding mycobacterial antigen (38 kDa) was achieved by the interaction of anti-Id TB71 with the T cell receptor complex (CD3/Ti). The accessory cell requirement in this response could not be replaced by anti-Id TB71 coupled to Sepharose beads and was not inhibited by Fc receptor blockade. When taken together with the finding that anti-Id TB71-induced proliferation of a T cell clone was restricted by determinants encoded by the major histocompatibility complex, these findings suggested that anti-Id TB71 was presented to 38-kDa antigen-reactive T cells by the same mechanisms as conventional antigenic determinants. That is, both stimulated T cells through the CD3/Ti complex and had to be presented in the context of class II molecules on accessory cells. The finding that the disruption of the integrity of the anti-Id TB71 combining site did not affect T cell responsiveness although antibody binding was ablated implied that anti-Id TB71 may be partially degraded and re-expressed with MHC class II determinants.

Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains.

“…The in vitro proliferation that is observed using monovalent Fab fragments or isolated H chains rules out the possibility that our anti-Id is causing proliferation of these primed cells by crosslinking receptors on the T cells, as has been described with the anti-CD3 antibody (19). This is consistent with other reports of anti-Id activating antigenprimed T cells (17,18). Kees et al (17) have shown that a rabbit anti-Id that mimics a 38-kD protein purified from Mycobacterium tuberculosis could stimulate human PBL obtained from either M. tuberculosis patients or BCG-vaccinated individuals.…”

“…The synthetic peptide S(139-147), which represents a partial a determinant epitope, could also stimulate anti-Id-primed T cells in vitro, further demonstrating the fidelity with which our anti-Id mimics the a determinant. It has been shown by others that anti-Id antibodies can influence specific T cell reactivity (15)(16)(17)(18). Thus, in the reovirus system, Sharpe et al (16) have demonstrated that an internal image anti-Id that was raised against an antireovirus type 3 mAb could trigger T cell immunity (delayed type hypersensitivity and CTL responses) to reovirus type 3 in naive mice.…”

“…Kees et al (17) have shown that a rabbit anti-Id that mimics a 38-kD protein purified from Mycobacterium tuberculosis could stimulate human PBL obtained from either M. tuberculosis patients or BCG-vaccinated individuals. It was determined that the proliferation elicited by the anti-Id was MHC restricted and dependent on interaction with APC (18).…”

Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7

“…It has been proposed that anti-idiotypic antibodies are taken up by dendritic cells in the skin, and presented to the immune system in association with class I and II major histocompatibility complex (MHC) glycoproteins, and costimulatory molecules 15. Cytotoxic and helper T cell responses capable of targeting the TAA that 105AD7 mimics may thus be elicited.…”

Function and Potentials of M. tuberculosis Epitopes

“…A special case of cross-reactivity is the induction of epitope-specific immune responses by anti-idiotype (Id) antibodies, acting as the epitope’s “internal image.” This was demonstrated for both mouse and human CD4 T-cell responses, using rabbit anti-Ids raised against PstS1-specific mouse mAbs (59, 60). However, the corresponding structural determinants remained undefined and the approach has been overtaken by the more exact recombinant DNA and synthetic peptide technologies.…”