Antigenic specificity of glutaraldehyde-treated rabbit albumin

Abstract

Rabbit albumin treated with glutaraldehyde is immunogenic in rabbits due to the new antigenic determinants induced into the molecule by glutaraldehyde (Onicǎ et al., 1978 a, b). Hardy et al. (1976 a, 1977) isolated quaternary pyridinium compounds from the acid hydrolysis products of glutaraldehyde-reacted ovalbumin, which are responsible for the strong chromophore absorbing at 265 nm exhibited by glutaraldehyde-treated proteins. Our data have shown that such structures are involved in the antigenic determinants of glutaraldehyde-treated rabbit albumin. As a consequence, the reaction between the modified albumin and the specific antibodies is inhibited by: (1) peptides with molecular weights of 7800 and 11,000 daltons, and having an absorption maximum at 265 nm, isolated from the pronase digest of glutaraldehyde-treated albumin; (2) compounds with pyridinium structures obtained by the reaction of glutaraldehyde and the amino groups of 6-aminohexanoic acid and (3) other proteins (human and bovine albumin, ovalbumin, rabbit immunoglobulin G, peroxidase) treated with glutaraldehyde. Since glutaraldehyde-treated albumin shows a reaction of identity with albumin aged in vivo or in vitro, it is possible that the physiologic aging of albumin involves the formation of pyridinium-like structures. The molecular rearrangements around such structures may represent the new antigenic sites specific for the aged albumin. These sites could be recognized as non-self by the immunocompetent cells, stimulating the production of physiologic autoantibodies which remove the modified albumin from the circulation.