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High-affinity immunoglobulin gamma Fc receptor I, commonly known as CD64, is a transmembrane glycoprotein that serves as a high-affinity receptor for the Fc portion of monomeric IgG (UniProtKB - P12314). It is primarily expressed on monocytes and macrophages, but its expression is significantly induced on neutrophils and specific subsets of dendritic cells during inflammatory or infectious states (PMID: 25324336). On dendritic cells, CD64 facilitates the capture and internalization of immune complexes, which is a critical step for antigen processing and subsequent presentation to T cells, thereby linking innate and adaptive immunity (PMID: 21637190). In clinical practice, the upregulation of CD64 on the surface of myeloid cells is a robust biomarker for the early detection of sepsis and systemic inflammation (StatPearls - CD64). Therapeutic strategies targeting CD64 include the development of bispecific antibodies that recruit CD64-expressing effector cells to eliminate tumor cells, as well as immunotoxins designed to selectively deplete activated CD64+ cells in chronic inflammatory conditions.
CD64-targeted therapies typically utilize the receptor's high affinity for IgG to either deliver cytotoxic payloads to activated myeloid cells or to bridge effector cells to tumor cells via bispecific antibodies. It also acts as a mediator for antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis of opsonized pathogens (PMID: 10799849).
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