Innate immune cells sense danger through a plethora of germline-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs) or cellular molecules that are exposed only by stressed, infected, malignant, or dead cells. Many of these danger-sensing receptors belong to the C-type lectin-like superfamily (CLSF) and therefore are called C-type lectin-like receptors (CTLRs). Certain activating CTLRs, namely, CLEC-2, Dectin-1, DNGR-1, NKp80, and NKp65, which are encoded by genes that are clustered together in a subregion of the mammalian natural killer gene complex (NKC), use a single copy tyrosine signaling module termed the hemi-immunoreceptor tyrosine-based activation motif (hemITAM). These hemITAM-bearing CTLRs are present on myeloid cells and innate lymphocytes and stimulate various functions, such as phagocytosis, cytokine production, and cytotoxicity. Proximal signaling mechanisms involve the tyrosine phosphorylation of the hemITAM and the subsequent activation of the kinase Syk. Signaling and Syk recruitment by the hemITAM appear to be tuned by variable amino acids within or near the hemITAM, which give rise to differences in downstream signaling events and diverging functional outcomes among hemITAM-bearing receptors.

先天性免疫细胞通过多种种系编码的受体来感知危险，这些受体识别与病原体相关的分子模式（PAMP）或仅暴露于受压，感染，恶性或死亡的细胞才能暴露的细胞分子。这些危险感知受体中的许多受体都属于C型凝集素样超家族（CLSF），因此被称为C型凝集素样受体（CTLR）。某些激活的CTLR，即CLEC-2，Dectin-1，DNGR-1，​​NKp80和NKp65，由簇集在哺乳动物自然杀伤基因复合体（NKC）子区域中的基因编码，使用单个拷贝酪氨酸信号传导模块称为基于半免疫受体酪氨酸的激活基序（hemITAM）。这些含hemITAM的CTLR存在于髓样细胞和先天淋巴细胞上，并刺激多种功能，例如吞噬作用，细胞因子的产生和细胞毒性。最近的信号传导机制涉及hemITAM的酪氨酸磷酸化和随后的激酶Syk的激活。hemITAM内或附近的可变氨基酸似乎可以调节hemITAM的信号传导和Syk募集，这会导致下游信号传导事件的差异以及携带hemITAM的受体之间功能结果的差异。