DEFINITION OF A TRICHOPHYTON PROTEIN ASSOCIATED WITH DELAYED-HYPERSENSITIVITY IN HUMANS - EVIDENCE FOR IMMEDIATE (IGE AND IGG4) AND DELAYED-HYPERSENSITIVITY TO A SINGLE PROTEIN

Dermatophytes of the genus Trichophyton cause infections of human skin , nails, and hair. Unlike most Ags, Trichophyton can elicit either imm ediate (IH) or delayed (DH) hypersensitivity skin reactions, Previous studies isolated a 30-kDa Ag (Tri t 1) that caused IH skin tests. The study presented here used skin testing and in vitro T cell proliferati on assays to monitor purification of an Ag, designated Protein IV, ass ociated with DH reactions. Protein IV was purified by cation exchange HPLC; amino acid sequence analysis of the N-terminus and nine internal peptides (143 residues) revealed no homologies to Tri t 1 or to any o ther known proteins. A mAb-based ELISA was developed to measure Protei n IV. Protein IV elicited DH skin reactions in subjects with a history of athlete's foot but also caused IH skin reactions. Serologic respon ses to Protein IV were studied in 59 adults who had been skin tested w ith Trichophyton extract. IH skin reactions were associated with a pos itive PAST (14/23) as well as with specific IgE (13/23) and IgC4 (14/2 3) Abs to Protein IV. DH skin tests were not associated with IgE or Ig G4 Abs, IgE anti-Protein IV Abs were quantitatively correlated with lg G4 Abs (r = 0.57, p < 0.001). Specific IgG Abs to Protein IV were high est in IH subjects (gm = 230 U/ml), and lowest in those with DH (gm 91 U/ml) or negative (gm = 81 U/ml) skin tests; furthermore, the prevale nce of IgG Abs increased significantly with age. Protein IV is the fir st defined protein associated with both DH and IH skin reactions; thes e reactions are characterized by distinct serologic responses. The res ults establish that diverse immune responses in humans can be directed against the same protein.