Antigen Recognition and the Immune Response

Abstract

Pursuant to the original observation that L-tyrosine-azobenzenearsonate (RAT, Table I) induced specific delayed hypersensitivity in guinea pigs (1), we demonstrated that this small molecule could serve as a carrier for macromolecular (2) or micromolecular (3) haptens. Indeed, the activity of RAT parallels that of conventional macromolecular immunogens. In addition to the induction of delayed cutaneous sensitivity, it triggered the release of migration-inhibitory factor and a proliferative response by cells from sensitized animals, and it prepared guinea pigs for secondary anti-hapten responses (2, 3).An investigation of the structural requirements for immunogenicity of RAT revealed that other charged moieties could substitute for arsonate, including trimethylammonium which has an opposite charge. Modifications at the arsonate position yielded immunogens with distinctive specificities (3). Preliminary findings with compounds modified at the tyrosine position indicated that one, but not both, charged groups were essential for immunogenicity (3).W e now present findings with a complete series of analogs of R A T modified at the tyrosine position, which have been used to explore the importance of charge and the size of hydrophilic and hydrophobic side chains for the immunogenicity of this molecule. Materials and Methods Antigens.--N-t-Butyloxycarbonyl-L-tyrosine was purchased from Bachem Co., MarinaDel Ray, Calif.; p-hydroxyphenylacetic acid, 3-(p-hydroxyphenyl)-propionic acid, tyramine, 4-N-propylphenol, 4-ethylphenol, and p-cresol were purchased from Aldrich Chemical Co., Milwaukee, Wis.; p-hydroxybenzoic acid was obtained from Eastman Kodak Co., Rochester, N. Y.; and p-hydroxyphenyl methyl carbinol was purchased from K & K Laboratories, Inc., Plainview, N. Y. These reagents were analyzed by thin-layer chromatography on silica gel and used without further purification, p-Hydroxyphenylethyl alcohol (tyrosol) was purchased from Research Organic Chemicals Co., Sun Valley, Calif., and purified by passage through a column of silica gel in ethyl acetate, followed by recrystallization in chloroform.

ABA‐T Determinant Regulation of Delayed Hypersensitivity

“…A great deal of careful research has been carried out with ABA-T and a wide variety of variations on this molecular theme in order to understand the unique immunogenic properties of this small family of molecules (Leskowitz 1963, Borek & Stupp 1965, Jones & Leskowitz 1965a, b, Colloti & Leskowitz 1970, Alkan et al 1971, 1972a, b, Mackler et al 1971, Bush et al 1972, Hanna & Leskowitz 1972, 1973a, b, Becker et al 1975, Bullock et al 1975a, b, c, Brunda & Raffel 1977, Prange et al 1977. A great deal of careful research has been carried out with ABA-T and a wide variety of variations on this molecular theme in order to understand the unique immunogenic properties of this small family of molecules (Leskowitz 1963, Borek & Stupp 1965, Jones & Leskowitz 1965a, b, Colloti & Leskowitz 1970, Alkan et al 1971, 1972a, b, Mackler et al 1971, Bush et al 1972, Hanna & Leskowitz 1972, 1973a, b, Becker et al 1975, Bullock et al 1975a, b, c, Brunda & Raffel 1977, Prange et al 1977.…”