Immunogenic sequences were found clustered in the RNA binding domains of A2/RA33. In immunized HLA-DR4 tg mice the reaction to A2/RA33 peptides seemed to be entirely produced by CD4+ T cells showing a Th1 phenotype, with some of the peptides inducing high production of IFN-γ. However, immunization of HLA-DR4 tg or DBA/1 mice with A2/RA33 protein induced only mild swellings in some animals with no pathological findings in the histological analysis. On the other hand, immunization of TNF tg mice enhanced arthritis significantly. These mice overexpressed A2/RA33 in the joint, whereas expression was very low in wild-type mice.