Analysis of lysozyme-specific immune responses by synthetic peptides. I. Characterization of antibody and T cell-mediated responses to the N-terminal peptide of hen egg-white lysozyme.

The immunological reactivity against the N-terminal region of hen egg-white lysozyme (HEL) has been investigated by a synthetic peptide (PHEL) comprising residue 1-18 of HEL and by an analogue peptide (PREL) in which phenylalanine at position 3 is substituted by tyrosine. Both peptides are immunogenic in (C57BL/10 X DBA/2)F1 mice genetically responder to HEL. In C57BL/6 mice, genetically nonresponder to HEL, PREL induces anti-peptide antibodies that also bind to PHEL whereas PHEL is not immunogenic. Thus, a single amino acid substitution in a synthetic peptide converts a nonresponder mouse strain into a responder one. Anti-PHEL antibodies demonstrate a higher binding to HEL than anti-PREL antibodies, indicating that phenylalanine at position 3 is important for induction of anti-peptide antibodies able to recognize native HEL. At the T cell level the two peptides show very high bidirectional cross-reactivity between themselves and with HEL for interleukin 2 production, antigen-specific proliferation and delayed-type hypersensitivity response, whereas conservation of phenylalanine at position 3 is required for induction of suppressor cells cross-reactive with HEL. This indicates that the N-terminal region of HEL contains epitope(s) able to induce the same level of helper T cell activity as the native HEL molecule. However, helper T cells do not discriminate between PHEL and PREL whereas phenylalanine at position 3 is critical for HEL-specific suppressor T cell induction.