Retrovirally Induced Mouse Anti‐TCR Monoclonals can Synergize the In Vitro Proliferative T Cell Response to Bacterial Superantigens

Abstract

Dehghanpisheh K, Marchalonis JJ. Retrovirally Induced Mouse Anti-TCR Monoclonals can Synergize the In Vitro Proliferative T Cell Response to Bacterial Superantigens. Scand J Immunol 1997;45:645-654 Antibodies directed against the b chain of the T-cell receptor (TCR) have been detected in animals and in humans in a number of distinct immune states that do not involve direct immunization with either T cells or TCR epitopes. When C57Bl/6 mice are infected experimentally with the LP-BM5 retrovirus mixture they produce increased titres of autoantibodies directed against TCR Vb complementarity determining region 1 (CDR1) epitopes. Here, the authors utilized hybridoma technology to isolate monoclonal immunoglobulin (Ig)M antibodies (MoAbs) that arose at the peak of infection. The authors characterized the binding specificity tested using synthetic peptides modelling the CDR1 segments of 24 distinct Vb gene products and determined the V H gene usage by two such monoclonals. One binds to a restricted set of TCR Vb CDR1 peptides, and the second reacts with approximately half of the CDR1 peptide homologues. These MoAbs are specific for T-cell receptor b chains and do not bind to immunoglobulin light chains or to unrelated protein molecules. Both MoAbs bind to intact T cells expressing the Vb domain (human Vb8 and mouse Vb11) from which selection peptides were derived, and costimulate a Vb specific in vitro T cell proliferative response induced by the staphylcoccal enterotoxin E (SEE) superantigen.

Circulating regulatory anti–T cell receptor antibodies in patients with myasthenia gravis

“…The fact that the titers of these anti-TCR Ab's increase not only in autoimmune diseases (experimental and human) (15,(17)(18)(19), but also during the course of viral infections (53)(54)(55) or alloimmunization (58), supports the concept that the increase in anti-TCR Ab titer may play a role not only in the regulation of autoimmune responses (and diseases), but also more generally in the regulation of any immune response. We are currently investigating this possibility in an immune response model to elucidate the possible function of anti-TCR Ab's in immunoregulation and their relationship to T reg cells.…”

“…In contrast, we detected a spontaneous increase in the levels of such Ab's in MG patients in the absence of immunization, consistent with the notion that these Ab's are induced naturally during the course of the disease. Other studies have reported the presence of Ab's against the CDR1 but not the CDR2 peptide in systemic lupus erythematosus and rheumatoid arthritis patients (15), and during the course of viral infection in mice and humans (53)(54)(55). These differences may be due to the arbitrary scanning of the whole TCR chain and the use of synthetic 16-mer peptides overlapping by five residues, an approach that may miss potential immunogenic regions (15,56).…”

Human monoclonal natural autoantibodies against the T‐cell receptor inhibit interleukin‐2 production in murine T cells

“…39 In our own studies with murine mAAbs to TCR Vb epitopes, we documented that such antibodies acted synergistically with superantigens in the activation of T-cell subsets. 24 Furthermore, studies using therapeutic preparations of purified human IgG document the immunoregulatory role of NAAbs in a variety of human diseases, with an anti-TCR specificity beneficial in Kawasaki's disease. 12 We have determined the affinity of one mAAb, OR2, for binding to the single-chain TCR and the CDR1 peptide on which all of the anti-TCR mAAbs were selected.…”

“…14,15,17,18 It has been proposed that NAAbs against the TCR may serve in immunoregulation of T cells. 24 This theory seems plausible given the nature of the specificity of these molecules and the understanding that antibodies play a critical role in neutralizing antigens through the interaction of the antibody-combining site with specific antigen. To test this premise, monoclonal NAAbs against the TCR are required to carry out the appropriate assays for determining their functional capacities.…”

Structural, antigenic and evolutionary analyses of immunoglobulins and T cell receptors

“…The role of natural autoantibodies to TCR Vb domains in immunomodulation is supported by observations that purified polyclonal human IgG (intravenous immunoglobulin; IVIG) has a therapeutic effect on Kawaski's disease (Kazatchkine and Kaveri, 2001), an inflammatory disease showing restricted Vb expression, and that IVIG modulates the expression of particular individual Vb gene segments in T cells induced by Staphyloccal enterotoxin B superantigen in vitro (Baudet et al, 1996). We were able to generate murine (Dehghanpisheh and Marchalonis, 1997) and human monoclonal antibodies against these markers. The murine monoclonals were synergistic with bacterial superantigens selective to different Vb subsets (Dehghanpisheh and Marchalonis, 1997).…”