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CD81 antigen

Definition:

Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking and compartmentalization of CD19 receptor on the surface of activated B cells. Upon initial encounter with microbial pathogens, enables the assembly of CD19-CR2/CD21 and B cell receptor (BCR) complexes at signaling TERMs, lowering the threshold dose of antigen required to trigger B cell clonal expansion and antibody production. In T cells, facilitates the localization of CD247/CD3 zeta at antigen-induced synapses with B cells, providing for costimulation and polarization toward T helper type 2 phenotype. Present in MHC class II compartments, may also play a role in antigen presentation. Can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes. Positively regulates sperm-egg fusion and may be involved in acrosome reaction (By similarity). In myoblasts, associates with CD9 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion of mononuclear cell progenitors into osteoclasts in charge of bone resorption (By similarity). May regulate the compartmentalization of enzymatic activities. In T cells, defines the subcellular localization of dNTPase SAMHD1 and permits its degradation by the proteasome, thereby controlling intracellular dNTP levels. Also involved in cell adhesion and motility. Positively regulates integrin-mediated adhesion of macrophages, particularly relevant for the inflammatory response in the lung (By similarity).; (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes. Association with CLDN1 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell.; (Microbial infection) Involved in SAMHD1-dependent restriction of HIV-1 replication. May support early replication of both R5- and X4-tropic HIV-1 viruses in T cells, likely via proteasome-dependent degradation of SAMHD1.; (Microbial infection) Specifically required for Plasmodium falciparum infectivity of hepatocytes, controlling sporozoite entry into hepatocytes via the parasitophorous vacuole and subsequent parasite differentiation to exoerythrocytic forms.

References:

[1]. Helen J Harris, et al. Claudin association with CD81 defines hepatitis C virus entry. J Biol Chem. 2010 Jul 2;285(27):21092-102. [Content Brief]

[2]. Anu Cherukuri, et al. B cell signaling is regulated by induced palmitoylation of CD81. J Biol Chem. 2004 Jul 23;279(30):31973-82. [Content Brief]

[3]. M R Schick, et al. The TAPA-1 molecule is associated on the surface of B cells with HLA-DR molecules. J Immunol. 1993 Oct 15;151(8):4090-7. [Content Brief]

[4]. Yoshito Takeda, et al. Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. J Cell Biol. 2003 Jun 9;161(5):945-56. [Content Brief]

[5]. Olivier Silvie, et al. Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity. Nat Med. 2003 Jan;9(1):93-6. [Content Brief]

[6]. Brandon Zimmerman, et al. Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket. Cell. 2016 Nov 3;167(4):1041-1051.e11. [Content Brief]

[7]. Menno C van Zelm, et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010 Apr;120(4):1265-74. [Content Brief]

[8]. Wei Yang, et al. An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry. FASEB J. 2015 Oct;29(10):4214-26. [Content Brief]

[9]. Joachim Lupberger, et al. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med. 2011 May;17(5):589-95. [Content Brief]

[10]. Vera Rocha-Perugini, et al. CD81 association with SAMHD1 enhances HIV-1 reverse transcription by increasing dNTP levels. Nat Microbiol. 2017 Nov;2(11):1513-1522. [Content Brief]

[11]. Tsipi Shoham, et al. Building of the tetraspanin web: distinct structural domains of CD81 function in different cellular compartments. Mol Cell Biol. 2006 Feb;26(4):1373-85. [Content Brief]

[12]. Sumudu K Narayana, et al. The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry. J Biol Chem. 2015 Oct 23;290(43):25946-59. [Content Brief]

[13]. Yael Sagi, et al. Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1613-8. [Content Brief]

[14]. V Rocha-Perugini, et al. CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses. Mol Cell Biol. 2013 Sep;33(18):3644-58. [Content Brief]

[15]. H Secrist, et al. Ligation of TAPA-1 (CD81) or major histocompatibility complex class II in co-cultures of human B and T lymphocytes enhances interleukin-4 synthesis by antigen-specific CD4+ T cells. Eur J Immunol. 1996 Jul;26(7):1435-42. [Content Brief]

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