Classic Hodgkin's lymphoma (HL)1 is a common malignant lymphoma characterized by the presence of a small population (Ͻ1%) of putative malignant cells, the morphologically distinct Hodgkin and Reed-Sternberg (HRS) cells. Recent advances in cell isolation techniques and molecular biology has identified Ig gene rearrangements within the majority of individual HRS cells, suggesting their B cell origin (1). These are surrounded by a large population of apparently non-malignant lymphocytes and histiocytes, whose proliferation is likely to be mediated by the wide range of cytokines and chemokines released by the HRS cells (reviewed in Refs. 2 and 3).HRS cells have many characteristics in common with antigen-presenting cells (APCs) such as activated B cells and dendritic cells (DCs) (4). Indeed, the HRS cell lines (L428, HDLM-2, and/or KM-H2) express cell surface molecules required for costimulation/proliferation of T cells (major histocompatibility complex class II, CD40, CD80, and CD86) (5-7), cell adhesion molecules involved in DC-T cell interactions (LFA-1, CD11c, and ICAM-1-3) (8, 9), and the DC-associated molecules (CD83 and fascin) (6, 10). They also produce inflammatory cytokines (e.g. tumor necrosis factor-␣ and lymphotoxin) (11), non-inflammatory cytokines (e.g. granulocyte macrophage-colony stimulating factor and interleukins 5 and 13) (12, 13), and chemokines (e.g. TARC) (14), which are associated with APCs. L428 cells have been used successfully in our laboratory to produce monoclonal antibodies (mAb) against DC differentiation antigens such as CMRF-44 (15) and and to clone the DC-associated molecules such as DEC-205 type I transmembrane multilectin receptor (17) and the adenosylhomocysteine hydrolase-like molecule DCAL/AHCYL-1 (18).We have investigated cell surface molecules on HRS cell lines with a view to identifying novel molecules related to APC function. These molecules might also be candidate targets for antibody-based HL immunotherapy. Indeed, CD20, CD25, and CD30 reagents (markers for B cells and activated lymphocytes) have been investigated in this regard (19 -21), but molecules more restricted to HRS cells might be preferred as targets for more specific therapeutics.During the cloning of DEC-205 from the L428 cell line by 3Ј-rapid amplification of cDNA ends (RACE) (17), we discovered an alternatively spliced novel DEC-205 mRNA. This mRNA encodes the intact DEC-205 ectodomain but included unique sequences encoding for an additional carbohydrate recognition domain (CRD) and a transmembrane (TM) and a cytoplasmic (CP) domain derived from a newly identified type I transmembrane C-type lectin DCL-1. A partial cDNA sequence