Tetraspanin CD53: an overlooked regulator of immune cell function

Tetraspanins are membrane organizing proteins that play a role in organizing the cell surface through the formation of subcellular domains consisting of tetraspanins and their partner proteins. These complexes are referred to as tetraspanin enriched microdomains (TEMs) or the tetraspanin web. The formation of TEMs allows for the regulation of a variety of cellular processes such as adhesion, migration, signaling, and cell fusion. Tetraspanin CD53 is a member of the tetraspanin superfamily expressed exclusively within the immune compartment. Amongst others, B cells, CD4⁺ T cells, CD8⁺ T cells, dendritic cells, macrophages, and natural killer cells have all been found to express high levels of this protein on their surface. Almost three decades ago it was reported that patients who lacked CD53 suffered from an increased susceptibility to pathogens resulting in the clinical manifestation of recurrent viral, bacterial, and fungal infections. This clearly suggests a vital and non-redundant role for CD53 in immune function. Yet, despite this striking finding, the specific functional roles of CD53 within the immune system have remained elusive. This review aims to provide a concise overview of the published literature concerning CD53 and reflect on the underappreciated role of this protein in immune cell regulation and function.