Applying the approach to the surface of cell lines representative of the lymphoid lineage, we observed that Trx1 basically targets a single cell surface protein, subsequently identified as TNF receptor superfamily member 8, also known as CD30. The pronounced preference of Trx1 for one particular target protein might seem surprising, but could be due to the fact that we assessed Trx1 reactivity of proteins as they are embedded in their natural microenvironment, namely the intact surface of the active plasma membrane of living cells. It is conceivable that protein disulfide exchange interactions are limited and controlled by their native context and location.