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- Xu, Yuekang, et al.
(författare)
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Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display : Implications for autoimmunity and molecular mimicry
- 2004
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Ingår i: Molecular Immunology. - Oxford : Elsevier. - 0161-5890 .- 1872-9142. ; 41:4, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- Two monoclonal antibodies (mAb) CB268 and CII-C1 to type II collagen (CII) react with precisely the same conformational epitope constituted by the residues ARGLT on the three chains of the CII triple helix. The antibodies share structural similarity, with most differences in the complementarity determining region 3 of the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by screening two nonameric phage-displayed random peptide libraries. For each mAb, there were phage clones (phagotopes) that reacted strongly by ELISA only with the selecting mAb, and inhibited binding to CII only for that mAb, not the alternate mAb. Nonetheless, a synthetic peptide RRLPFGSQM corresponding to an insert from a highly reactive CII-C1-selected phagotope, which was unreactive (and non-inhibitory) with CB268, inhibited the reactivity of CB268 with CII. Most phage-displayed peptides contained a motif in the first part of the molecule that consisted of two basic residues adjacent to at least one hydrophobic residue (e.g. RRL or LRR), but the second portion of the peptides differed for the two mAbs. We predict that conserved CDR sequences interact with the basic-basic-hydrophobic motif, whereas non-conserved amino acids in the binding sites (especially HCDR3) interact with unique peptide sequences and limit cross-reactivity. The observation that two mAbs can react identically with a single epitope on one antigen (CII), but show no cross-reactivity when tested against a second (phagotope) indicates that microorganisms could exhibit mimics capable of initiating autoimmunity without this being evident from conventional assays. © 2004 Elsevier Ltd. All rights reserved.
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- Carlsson, Robert, et al.
(författare)
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SPI-C, a PU-box binding ETS protein expressed temporarily during B-cell development and in macrophages, contains an acidic transactivation domain located to the N-terminus.
- 2003
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Ingår i: Molecular Immunology. - 1872-9142. ; 39:16, s. 1035-1043
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient for SPI-group ETS transcription factors PU.1 or SPI-B fail to generate lymphocytes or do not mount normal antibody mediated immune responses, respectively. PU.1 expression is restricted to B-, T-lymphocytes and macrophages, while SPI-B is expressed in B- and T-lymphocytes. SPI-C is an ETS transcription factor closely related to PU.1 and SPI-B, and expressed temporarily during B-cell development and in macrophages. By deletion and mutation analysis we show that the SPI-C protein has a transactivation domain located to the N-terminus, and that the transactivation activity is reduced to that of the DNA binding domain (DBD) alone when four aspartic acid residues are mutated to alanines. PU.1 and SPI-B regulate transcription from acidic domains located to the N-terminus and by recruiting the co-activator PIP to adjacent sites in a sequence specific manner. In contrast to PU.1 and PIP, SPI-C and PIP were unable to form a distinct ternary complex on the Ig λ light chain λ2–4 enhancer element, suggesting that SPI-C could act both as a positive and negative transcriptional regulator during B-lymphocyte differentiation.
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