Dysfunctional immune synapses in T cell immunodeficiencies

Adaptive immune responses take place in the T cell area of secondary lymphoid organs, where, on encounter of antigen-presenting cells (APCs) bearing specific MHC-associated antigen, T lymphocytes assemble a highly organized intercellular junction, referred to as the immune synapse, on which T cell activation, proliferation, and differentiation crucially depend. Immune synapse assembly and function are impaired in a subgroup of human immunodeficiencies, characterized by altered adhesion or defective cross talk between the two synaptic partners. In this chapter, we will provide an overview of the immune synapse and describe how dysfunctional immune synapses can impinge on the pathogenesis of T cell immunodeficiencies, highlighting the reciprocal contribution of alterations at either side of the IS.