Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones.
In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These findings demonstrate that alpha, beta-unsaturated ketones form antigens after a nucleophilic attack at the beta-carbon with soft nucleophiles such as thiol in cysteine and not with the formation of a Schiff's base after a nucleophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermore, no cross-reactivity was observed between R- and S-carvone indicating the importance of the 3-dimensional structure of haptens (and antigens) in T-cell recognition. The analogues were also tested for cross-reactivity on patients allergic to carvone. The results from the animal study were confirmed.
Nilsson
A M
AM
Occupational Dermatology, National Institute for Working Life, Stockholm, Sweden.
Gäfvert
E
E
Salvador
L
L
Luthman
K
K
Bruze
M
M
Gruvberger
B
B
Nilsson
J L
JL
Karlberg
A T
AT
D000485:Allergens / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D003429:Cross Reactions; D000081005:Cyclohexane Monoterpenes; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D017453:Dermatitis, Irritant / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D039821:Monoterpenes; D010328:Patch Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000276:immunology*
D000485:Allergens; D000941:Antigens; D000081005:Cyclohexane Monoterpenes; D007659:Ketones; D039821:Monoterpenes; D013729:Terpenes; C006923:carvone