Allergic arthritis induced by cationic antigens: relationship of chronicity with antigen retention and T-cell...

In order to define the antigenic properties necessary for sustained allergic arthritis, we prepared a range of differently charged bovine serum albumin (BSA) species with increasing isoelectric points (4.5, 4.5-7.4, 7-8, 8.5-9 and greater than 9). The highly cationic BSA greater than 9 appeared to be in a polymeric form. We investigated three properties of these proteins: (i) antigen retention, (ii) T-cell reactivity, and (iii) arthritis induction. Injection of the respective radiolabelled antigens in the knee-joints of immunized mice showed that antigen retention increased with cationicity of the proteins, with the best retention found for BSA with pI greater than 9. However, sustained joint inflammation was only found with BSA8.5-9, and not with a level BSA of lower or even higher pI. T-cell reactivity in vivo as measured by delayed-type hypersensitivity (skin testing) was similar for the tested antigens, with the exception of polymeric BSA (greater than 9). The latter appeared to be a poor antigen. In vitro, T-cell reactivity ([3H]-thymidine incorporation) against the cationized BSA species was slightly higher as compared to native BSA. The combination of excellent antigen retention and adequate T-cell reactivity appears to be optimal for the induction of chronic arthritis.