Induction of antibodies against a peptide hapten does not require covalent linkage between the hapten and a class II presentable T helper peptide

Abstract

Following immunization with a complex antigen, a B cell internalizes this antigen through an interaction between its surface immunoglobulins and an epitope of the antigen. Enzymatic processing of the antigen frees one or more short peptide determinants (TD) which bind to class II molecules of the B cell. If the complex TD-MHC II is recognized by the receptor of a T helper cell, T cell help is provided leading to the expansion of an antibody-producing B cell clone specific for the epitope. We present experimental evidence proving that the induction of anti-peptide hapten antibodies does not require covalent linkage between the peptide hapten and the peptide behaving as TD. Indeed, high anti-peptide hapten antibody titers are induced if an emulsion of TD and hapten are injected in the same immunization site. This result suggests a way to manipulate antibody production with useful applications to research and therapy.

Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection

“…As demonstrated previously by our laboratory, it is possible to induce antibodies against a peptide hapten or protein hapten by immunization with a mixture of FIS and the haptenic peptide (or protein) not covalently linked (8,9). This prompted us to treat chronic WHV infection by attempting to induce anti-WHs antibodies in nine chronically WHV-infected woodchucks.…”

“…1) we tested our hypothesis by immunizing woodchucks with WHsAg in conjunction with FIS, a TDh peptide from sperm whale myoglobin well recognized by several class II restrictions (7)(8)(9)28,29) or with HBs120_134, another TDh peptide also described as being recognized by several class II molecules (30). Woodchuck 310 (Fig.…”

“…The vaccines used were plasma-derived HBsAg (4,5) or recombinant HBsAg containing preS2 sequences (6). In the study by Dien-Our laboratory has made attempts to develop strategies to induce humoral (7)(8)(9) and cytotoxic (10,11) responses using synthetic peptides. We have shown (9) that SJL/J mice, normally non-responders to HBsAg, can be rendered responders by joint immunization with HBsAg and a T helper cell determinant peptide (TDh) encompassing residues 106-118 from sperm whale myoglobin (from now on designated FIS).…”

Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct

“…Another aspect concerning the induction of CTL in vivo is whether the TD, and TD,, need to be covalently linked to induce CTL, or perhaps it might suffice to prime with a mixture of them, a result that might resemble the induction of antibodies using another type of peptide constructs (7). Comparison of Figs.…”

“…Our understanding of how T-cell help is provided to antibody producing B-cells has greatly benefited from immunization studies using peptide haptens linked to a peptide determinant sequence (TDJ2 recognized by T-cells (1)(2)(3)(4)(5)(6) as well as by immunization with mixtures of hapten and TD,, molecules injected in the same immunization site (7).…”