Down‐regulation of antigen‐specific antibody production by TCR antagonist peptides in vivo

• Published in: European journal of immunology Vol. 30; no. 2; pp. 403 - 414
• Main Authors: Toda, Masako, Totsuka, Mamoru, Furukawa, Shigetada, Yokota, Kahori, Yoshioka, Tohru, Ametani, Akio, Kaminogawa, Shuichi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.02.2000
• Subjects: Cross‐reactivity; IgE production; Immunointervention; Specific Ab response; TCR antagonist
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200002)30:2<403::AID-IMMU403>3.0.CO;2-8

The efficacy of TCR antagonist peptides in inhibition of antigen‐specific antibody production and T cell responses in vivo was evaluated. Among amino acid‐substituted analogs of a peptide corresponding to residues 119 – 133 of bovine β‐lactoglobulin (p119 – 133), pR124Q and pD129S, prepared by substitution of Gln and Ser for Arg124 and Asp129, respectively, have been shown to display TCR antagonist activity for three out of four distinct p119 – 133‐specific T cell clones and for polyclonal T cells derived from p119 – 133‐immunized C57BL / 6 mice. Both pD129S and pR124Q inhibited in vivo priming and subsequent activation of T cells by p119 – 133 when co‐injected with p119 – 133 into mice, as shown by the decreased proliferation of T cells in response to p119‐133 in vitro. pD129S significantly inhibited production of anti‐p119 – 113 antibodies of IgG1, IgG2b and IgE isotype in vivo when co‐injected into mice together with p119 – 133 at the time of the first immunization. However, pR124Q was totally ineffective in inhibition of the antibody responses. Anti‐p119 – 133 antibodies from p119 – 133‐immunized mice could bind to pR124Q but not to pD129S, suggesting that the difference in cross‐reactivity is responsible for the different effect of these two peptides on specific antibody production. Our findings demonstrate that a single TCR antagonist peptide can inhibit antigen‐specific polyclonal antibody production when this antagonist peptide does not cross‐react with the antibody elicited in response to an antigenic peptide.