Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 0.5% of the global population. Despite its prevalence, there is no known cure, underscoring the persistent need for novel therapeutic strategies. In previous studies, we identified a specific subset of antibodies that target an epitope (F4) on type-II collagen (COL2), which seemed to offer protection against arthritis. Leveraging these findings, we have engineered a range of recombinant antibodies against this epitope. Notably, one such antibody, R69-4, has shown significant potential in suppressing arthritis. Here, we aim to identify potential cross-reactive targets of R69-4 to better understand its mechanism of action.