Compositions and methods are provided for diagnosis and treatment of rheumatoid arthritis. Defects in T cell receptor signaling lower the activation threshold of RA T cells, thus predisposing for a failure in maintenance of immune tolerance. Overexpression of B-Raf and/or K-Ras in CD4 T cells lowers the threshold to respond to TCR triggering in the absence of costimulation and increases responses to citrullinated peptides and other autoantigens.
