Receptors for the Fc region of IgG (Fc gamma Rs) are members of the Ig superfamily that function in the activation or inhibition of immune responses such as degranulation, phagocytosis, ADCC (antibody-dependent cellular toxicity), cytokine release, and B cell proliferation (1-3). The Fc gamma Rs have been divided into three classes based on close relationships in their extracellular domains; these groups are designated Fc gamma RI (also known as CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16). Each group may be encoded by multiple genes and exist in different isoforms depending on species and cell type. The CD64 proteins are high affinity receptors
(~10-8-10-9 M) capable of binding monomeric IgG, whereas the CD16 and CD32 proteins bind IgG with lower affinities (~10-6-10-7 M) only recognizing IgG aggregates surrounding multivalent antigens (1, 4). Fc gamma Rs that deliver an activating signal either have an intrinsic immunoreceptor tyrosine-based activation motif (ITAM) within their cytoplasmic domains or associate with one of the ITAM-bearing adapter subunits, Fc R gamma or zeta (3, 5). The only inhibitory member in human and mouse, Fc gamma RIIb, has an intrinsic cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM). The coordinated functioning of activating and inhibitory receptors is necessary for successful initiation, amplification, and termination of immune responses (5).
Human CD16 is encoded by two genes; Fc gamma RIIIA is an activating transmembrane receptor expressed in macrophages and NK cells, and Fc gamma RIIIB is a GPI-linked protein on granulocytes (2). Mouse Fc gamma RIII and human Fc gamma RIIIA share 44% amino acid identity and are frequently described as functional equivalents (5).
CD16-2, also referred to as Fcg R4, is a protein that is more closely related to human Fc gamma RIIIA (60% amino acid identity) and may be its true ortholog (6). Similar to other activating receptors, it possesses a charged residue within its transmembrane domain that is necessary for association with an ITAM bearing accessory protein. CD16-2 RNA expression was observed in peripheral blood leukocytes, spleen, thymus, colon, and intestine.
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| Product By Gene ID | 246256 |
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