Disease relevance of Id

• Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id) [1].
• Shared idiotypes (Ids) were identified on monoclonal antibodies specific for different immunodominant sugars in the lipopolysaccharide (LPS) of Gram-negative bacteria [2].
• The Id could be shown to react with a Theiler murine encephalomyelitis virus strain WW which was isolated from mice after inoculation with periplaque white matter from brain in a histologically confirmed case of MS [3].
• Multiple myelomas produce tumor-specific antigen (TSA) in the form of idiotype (Id) on monoclonal Ig [4].
• The Id could not be detected in three cerebrospinal fluid samples and 28 serum samples of heterologous MS patients or in the serum of 43 optic neuritis patients [3].

High impact information on Id

• When the disulfide bond is reduced by an activity present in muscle cell lysates or disrupted by site-directed mutagenesis, the monomeric form of the protein is strongly favored at 37 degrees C. These E2A monomers cannot bind DNA but heterodimerize efficiently with Id and MyoD [5].
• HLH forced dimers: tethering MyoD to E47 generates a dominant positive myogenic factor insulated from negative regulation by Id [6].
• Mesenchymal Gremlin expression is lost in limb buds of mouse embryos homozygous for the limb deformity (Id) mutation, which disrupts establishment of the SHH/FGF4 feedback loop [7].
• Inhibition of myeloid differentiation by the helix-loop-helix protein Id [8].
• When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon gamma than spleen cells from mice neonatally injected with HSS Id or NoMoIgG [1].

Chemical compound and disease context of Id

• In addition, the binding of labeled MOPC-167 to anti-A48 Id antibodies was not inhibited by PC but was inhibited by A48 and 3-76-42 MAb bearing A48, UPC-10 non-antigen-inhibitable idiotopes [9].
• Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) or anti-TEPC 15 idiotype (T15Id) antibody specific for the major idiotype (Id) of anti-PC antibody [10].
• Cycloheximide did not block the vitamin D suppression of Id message level [11].
• J1-8-1 heavy chain had an NH2-terminal amino acid sequence identical to that of 11-4.1 for the 39 NH2-terminal residues assigned, whereas its light chain and the heavy and light chains of the other Id' molecules differed markedly from those of the 11-4.1 antibody [12].
• We have recently shown that doxorubicin (Dox), an antineoplastic drug and an inhibitor of terminal differentiation of myogenic and adipogenic cells, induces expression of Id, a gene encoding a helix-loop-helix transcriptional inhibitor [13].

Biological context of Id

• Comparisons of the amino acid sequence of the UPC-10 and A48 VH regions, and the distribution of the A48 Id family on A48, UPC-10, and three MAb, suggested that A48 regulatory idiotypes can be located on the framework segment of VH region [9].
• To pursue the molecular basis for the frequency of Id 16/6, we have analyzed polymerase chain reaction-generated C mu, C gamma, and VH3 family V gene libraries derived from the circulating and tonsillar B cells of four normal individuals and from the B cells of two patients with active systemic lupus erythematosus (SLE) [14].
• Northern blot analysis showed that impaired differentiation was associated with delayed up-regulation of MyoD and myogenin and delayed down-regulation of Id, a dominant negative inhibitor of differentiation [15].
• Therefore, these data suggest that the altered expression of Pax-5, but not E2A or Id, is responsible for the loss of CD19 expression in human myeloma cells, although the underlying mechanism of the altered Pax-5 gene expression remains to be clarified [16].
• The idiotopic (Id) repertoire of antibody response to phosphocholine was studied in mouse strains with different IgH allotypes [17].

Anatomical context of Id

• To investigate the nature of these Id' molecules, spleens from such anti-idiotype-treated mice were fused with the SP2/0 myeloma to produce monoclonal Id' antibodies [12].
• We have shown that mutated regions of lymphoma Id contain MHC class I binding peptides that are potential targets for cytotoxic T cells [18].
• In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate [19].
• We have previously reported the overexpression of inhibitor of DNA binding/differentiation (Id) in the endothelial cells within the synovial tissues of rheumatoid arthritis [20].
• The amino acid sequence predicted from the nucleotide sequence of the VKJK from Xmp-specific CRIXmp-1+ hybridomas is identical to the sequence of the anti-arsonate antibody 1210.7, which is the prototype of another Id family (CRI) that is conserved and dominant in BALB/c mice [21].

Gene context of Id

• These novel observations indicate a coordinate expression and function of an inhibitory Id protein (Id2) and a stimulatory bHLH/bHLH heterodimer (TAL1/E2A) in normal erythroid differentiation [22].
• Cotransfection experiments showed that activation by INSAF was inhibited by Id, a negative regulator of basic helix-loop-helix (bHLH) protein function [23].
• In an anti-SEA ELISA, MSS and HSS Id preparations contained comparable levels of IgM and IgG1 [24].
• MyoD activity was also inhibited by Id, a HLH protein, and this inhibition was reversed by the addition of excess E12 or MITF-2A [25].
• Overexpression of Id enhanced expression of ICAM-1 and E-selectin, and induced angiogenic processes such as transmigration, matrix metalloproteinase-2 and -9 expression, and tube formation [20].

Analytical, diagnostic and therapeutic context of Id

• Secondly, the panels of sera were also tested in a direct binding ELISA to detect partially cross-reactive Id that may not have been identified in the inhibition radioimmunoassay without differing results [26].
• Adoptive transfer of C.B-20 anti-BCL1 Id splenocytes into irradiated recipients that prevented an anti-H-40 response due to H-40 tissue expression failed to adoptively confer BCL1 immunity [27].
• Southern blot restriction analysis and nucleotide sequence analysis of the expressed genes used by three TGB5 Id+ 2 degrees HP showed usage of three different VH genes in two VH gene families (36-60 and J558), different D segments, and two different Vk1 genes (the Vk1A and Vk1C subgroups) [28].
• OBJECTIVE: To evaluate the potential of a monoclonal proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) antiidiotype autoantibody (5/7 anti-Id) as a candidate for specific immunotherapy in Wegener's granulomatosis (WG), and to estimate the immunodiagnostic value of the corresponding idiotype (5/7 Id) [29].
• By direct radioimmunoassay binding, competition of Id binding and Western blot anti-H62 and anti-L62 antibodies identify as Id-positive the same group of IgG1, bind in a reciprocal fashion to H- and L-chains of parental monoclonal antibody 62, and detect Id62-positive polyclonal serum autoantibodies to thyroglobulin [30].

References