Rheumatoid arthritis patients were found to have CD4+ T cells that proliferate in response to autologous synovial fluid and plasma. T cell clones and polyclonal T cell lines were found to respond to antigen(s) eluted from protein A Sepharose and anti-human immunoglobulin (Ig) antibody Sepharose. The antigen(s) was further resolved to fractions that contained intact Ig or Ig heavy chain since the T cells responded to > 100 kDa and 40-60 kDa polypeptides derived from purified Ig under nonreducing and reducing conditions, respectively. These results indicated that the antigen(s) is either Ig heavy chain or Ig-binding proteins that copurify with Ig and Ig subunits. Pepsin and papain digestion of the antigenic fractions eluted from protein A destroyed the T cell reactivity. Since most Fab regions are resistant to these enzymes, further analyses are required to localize the antigenic epitope(s). The presence of Ig- or Ig-antigen complex-reactive T cells in arthritic joints implies that B cells expressing anti-Ig antibody (i.e. rheumatoid factor) may play an important role in antigen presentation to autoreactive T cells.