Structural peculiarities of a truncated V kappa III immunoglobulin light chain in myeloma with light chain deposition disease.
We report on the primary sequence of the monoclonal immunoglobulin light chain (LC) REV involved in myeloma-associated light chain deposition disease (LCDD). This sequence was deduced from that of the corresponding complementary (c)DNA in bone marrow plasma cells. Products of three independent amplifications by polymerase chain reaction (PCR) were sequenced and found to be identical. The kappa mRNA encoding this N-glycosylated LC showed an overall normal structure consisting of a V kappa III segment rearranged to J kappa II. Direct N-terminal amino acid sequencing of the circulating monoclonal IgA2, kappa showed identity with the bone marrow-derived sequence. The kappa-chain presented several unusual features affecting both the leader sequence and the variable (V) region. Four unique amino acid substitutions were found at positions -8, -3, -2 and -1 in the leader sequence and probably resulted in an unusual cleavage by signal peptidase, thus making the LC truncated by one residue and accounting for its unique hydrophobic N-terminus: Ile-Ile-Leu. Additional peculiarities were observed in the V region, including a Thr74-->Asn substitution creating a N-glycosylation site, and Thr53-->Ile, which was only reported once among human kappa III chains, in another LCDD case, and may be of special significance at a position usually harbouring a polar amino acid.
Decourt
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Laboratoire d'Immunologie et d'Immunogénétique, CNRS EP J0118, Faculté de Médecine, Limoges, France.
Cogné
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Rocca
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A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001853:Bone Marrow; D017931:DNA Primers; D015321:Gene Rearrangement / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D010265:Paraproteinemias / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D007070:Immunoglobulin A; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D021382:Protein Sorting Signals; D012333:RNA, Messenger