Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in mice treated with the dominant T-cell epitope peptides.

BACKGROUND: Mice treated with the dominant T-cell epitope peptides of allergens were reported to have reduced peptide or allergen-specific T-cell responses on subsequent immunization, but the extent of reduction of allergen-specific antibodies is not clear. OBJECTIVE: This study was done to compare the extent of reduction of T-cell and antibody responses in peptide-treated mice. Two allergens were tested. Bee melittin (Api m 4), an allergen of 26 amino acid residues, has a single dominant T- or B-cell epitope. Hornet antigen 5 (Dol m 5), an allergen of 204 amino acid residues, has multiple dominant T- or B-cell epitopes. METHODS: Mice were treated with T-cell peptides of Api m 4 or Dol m 5 and then immunized biweekly with their respective allergen with alum adjuvant. T-cell peptides tested were residues 7-19 of Api m 4 and residues 41-60, 141-160, and 176-195 of Dol m 5. T-cell responses at week 9 or 11 were assayed by proliferation of spleen cell cultures. Antibody responses of different isotypes were measured biweekly by ELISA. RESULTS: Partial reduction of 30% to 50% of T-cell responses to peptide or allergen was observed in bee and hornet peptide-treated mice. About 65% reduction of Api m 4-specific antibody response was observed early in the immune response but gradually subsided to about 40% late in the response. Partial reduction of about 40% of Dol m 5-specific antibody response was only observed early in the immune response. CONCLUSION: Peptide treatment is partially effective in the reduction of T-cell responses of univalent or multivalent allergens. It is also partially effective in the reduction of antibody response of a univalent allergen, but it is poorly effective for a multivalent allergen.

A solution to the rheumatoid factor paradox: pathologic rheumatoid factors can be tolerized by competition with natural rheumatoid factors.

Rheumatoid factors (RF) associated with arthritic joint erosion are only seen transiently, if at all, in nondiseased individuals. Therefore, a tolerance mechanism must exist that prevents pathologic RF B cells from expressing Abs. Surprisingly, it has been shown that pathologic RF B cells are not tolerized by any previously established tolerance mechanism such as deletion, receptor editing, anergy, or prevention of memory establishment. How are pathologic RF cells tolerized? By simulating the RF response with a cellular automaton model immune system, we demonstrate that pathologic RFs can be tolerized by the novel mechanism of "competitive tolerance" with natural, nonpathologic RFs. We then demonstrate that competitive tolerance can be broken when a sequestered pool of expanding B cells are inappropriately subjected to chronic stimulation (as appears to occur in MRL/lpr mice and in patients with rheumatoid arthritis).