Longstanding immunological dogma holds that flexible immune recognition, which forms the mechanistic basis of adaptive immunity, is strictly confined to the lymphocyte lineage. In higher vertebrates, flexible immune recognition is represented by recombinatorial antigen receptors of enormous diversity known as immunoglobulins, expressed by B lymphocytes, and the T cell receptor (TCR), expressed by T lymphocytes. The recent discovery of recombinatorial immune receptors that are structurally based on the TCR (referred to as TCR-like immunoreceptors, "TCRL") in myeloid phagocytes such as neutrophils and monocytes/macrophages now challenges the lymphocentric paradigm of flexible immunity. Here, we introduce the emerging concept of "extralymphocytic flexible immune recognition" and discuss its implications for inflammation and aging.
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