Induction of Allergen-Specific T Cells by Conjugates of N-Formyl-Methionyl-Leucyl-Phenylalanine and Rye Grass Pollen Extract

Abstract

A conjugate of the biologically active peptide N-formyl-methionyl-leucyl-phenylalanine and rye grass pollen extract (F-MLP/rye), previously shown to react with rye grass pollen extract-specific T cells, induced the formation of allergen-specific T cells in mice. Lymph node cells prepared from mice immunized with either native extract or F-MLP/rye gave an enhanced response to unmodified rye grass pollen allergens in vitro. Syngeneic spleen macrophages were able to present the unmodified allergens to T cells obtained from both groups of mice causing their proliferation in vitro. Conjugation of the peptide into the extract brought about an extensive reduction in its reactivity with grass pollen-specific human IgE, and a loss of its ability to induce specific IgG antibody in guinea-pigs. A state of delayed hypersensitivity specific for rye grass pollen extract was produced in guinea-pigs by immunization with either the F-MLP/rye or unmodified extract. It is concluded that conjugates such as F-MLP/rye or other T′ allergoids could be used as probes to investigate whether changes in T cell activity are important in immunotherapy.

Retained T-Cell Reactivity of Rye Grass Pollen Extract following Cleavage with Cyanogen Bromide and Nitrothiocyanobenzoic Acid

“…For example, conju gates of polysarcosine and extract were shown to suppress the induction of murine IgE antibody re sponses via T-suppressor cell mechanisms [19]. Re cently we have shown that accessory cell-processed al lergen fragments produced by chymotryptic fission can stimulate T cells, and can also induce helper cells which collaborate with hapten-specific B cells in an adoptive transfer system [17], Conjugates between formyl-methionyl-leucyl-phenylalanine and extract were similarly presented by accessory cells and could induce delayed hypersensitivity in guinea pigs [3,20], In contrast to these results, the extract fragments, pro duced by fission with chemical reagents described here neither induced T cells which were able to collab orate in an adoptive transfer system nor gave delayed hypersensitivity reactions in guinea pigs; yet they were active in both murine and human lymphocyte proliferation assays.…”