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

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.