Figure 1.

Schematic representation of defective identified pathways in immunodeficiencies predisposing to high susceptility to Epstein–Barr virus (EBV)-driven B-cell lymphoproliferative diseases. Defective components in the pathways are in yellow. Three non-redundant pathways have been shown to be impaired: the SLAMF6/2B4/SLAM-associated protein (SAP) pathway, the CD70/CD27 pathway, and the NKG2D/MICA/MAGT1 pathway. At some point, several of these pathways may converge toward distal effector molecules such as RASGRP1 and CTPS1 that are required for expansion of T cells. The connection of CORO1A to these pathways is not known. Besides the essential role of CD8⁺ T cells, NK and iNKT cells which are often decreased in these primary imunodeficiencies may play a role in the immune response against EBV, particularly during the early phase of the primary infection. Vγ9δ2 T cells are also thought to play an important role in the primary infection by recognition of latently EBV-replicating B cells.