Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings.

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IntroductionNotch proteins are a family of ligand-activated large (300 kDa) single-pass transmembrane heterodimeric receptors. 1 Notch controls multiple cell fate decisions and differentiation processes during lymphocyte development and function and is required at various stages of T-cell development. 2,3 Deregulated Notch signaling during T-cell development leads to malignant transformation, including the cancer most closely associated with aberrant Notch expression in humans, acute T-cell acute lymphoblastic leukemia (T-ALL), which constitutes approximately 15% to 20% of ALLs seen in adults and children. 4,5 The oncogenic potential of Notch was first identified in (t7;9) chromosomal rearrangement in approximately 2% of human T-ALL, whereby intracelluar Notch1 is translocated to the T-cell receptor (TCR) ␤ gene. 6 More than 50% of human T-ALLs bear mutations in Notch1, indicating a prominent role for Notch in this T-cell malignancy. 7 Inhibitors of Notch signaling abrogate the growth of human and murine T-ALL cell lines bearing Notch1 gain-of-function mutations, indicating Notch is required in established tumors. 8,9 In vertebrates, 4 notch receptors (Notch 1-4) are activated by 5 different Notch ligands expressed on various cell types: Jagged1, Jagged2, and Delta-like (DL)1, DL3, and DL4. 2,3 After ligandbinding, proteolytic cleavage by ␥-secretase releases the signalingcompetent intracellular domain of Notch (N IC ). 10-12 N IC is composed of a RAM domain, ankyrin repeats (ANK) that mediate protein-protein interactions, nuclear localization sequences, a transactivation domain (TAD), and a C-terminal PEST domain regulating protein turnover. Human T-ALL cases frequently bear activating mutations in the extracellular heterodimerization domain and/or the C-terminal PEST domain of Notch1, resulting in ligand-independent activation. 7 During canonical Notch signaling, N IC translocates to the nucleus, engages its nuclear binding protein CSL (CBF-1, mammals; suppressor of hairless, Drosophila melanogaster; Lag-1, Caenorhabditis elegans) and transcribes downstream target genes, including the HES family of transcriptional repressors. 13,14 In the absence of N IC , CSL recruits repressor complexes to the regulatory regions of Notch/CSL target genes, inhibiting transcription. N IC interaction with CSL acts as a switch that promotes the assembly of CSL coactivator complexes. [15][16][17] ␥-Secretase inhibitors (GSIs) block proteolytic cleavage of Notch receptors, thereby preventing activation of Notch. Use of GSI in activated T cells results in down-regulation of nuclear factor (NF)-B activity, cytokine (interleukin-2 [IL-2] and interferon-␥ [IFN-␥]) production, and cell proliferation. 18 In T-cell lymphomas, context-specific putative target genes have been identified through which Notch1 may promote transformation by altering cell-growth kinetics. [19][20][21] The D-type cyclins (cyclins D1, D2, and D3) are the first cyclins to be induced as cells enter the G 1 phase of the cell cycle, [22][23][24] and, thus, if regulat...

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