Abstract
The human CD30 molecule is expressed transiently at very low levels on intrafollicular and perifollicular T and B cell blasts in lymphoid tissues, but is specifically upregulated on certain tumor cells, e.g. Hodgkin and Reed–Sternberg (H‐RS) cells. With its specific expression pattern and easy accessibility on the surface of H‐RS cells CD30 is a valuable diagnostic marker and holds considerable promise as a target for in vivo immunotherapy. Knowledge of epitopes on the CD30 molecule is expected to facilitate the design of novel non‐immunogenic anti‐CD30 reagents. Therefore, we have mapped the epitopes of several monoclonal antibodies (mAb) applying a peptide array of overlapping CD30‐derived peptides. For the mAb Ber‐H2, two linear epitopes with identical sequence were found, while the mAb Ki‐2 and the single chain Fv fragment R4‐4 each recognized a single linear antigenic determinant, respectively. On the other hand, the mAb Ki‐1 bound to a discontinuous epitope composed of two regions, one located near the N‐terminus and the other near the membrane‐spanning region of CD30. Using molecular modeling, it was possible to visualize the location of the epitopes on exposed loop regions of the molecule within the N‐terminal domain. Finally, the results obtained with the mAb Ki‐1 imply that the ends of the N‐ and C‐terminal parts of the extracellular portion of CD30 are in close vicinity of each other, suggesting a flower‐like structure for the membrane‐bound homotrimeric CD30 molecule. Copyright © 2003 John Wiley & Sons, Ltd.