Structural peculiarities of a truncated V kappa III immunoglobulin light chain in myeloma with light chain deposition disease

Clin Exp Immunol. 1996 Nov;106(2):357-61. doi: 10.1046/j.1365-2249.1996.d01-841.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Bone Marrow
  • DNA Primers
  • Gene Rearrangement / genetics
  • Genes, Immunoglobulin / genetics
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / genetics*
  • Immunoglobulin kappa-Chains / immunology
  • Molecular Sequence Data
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / immunology
  • Paraproteinemias / genetics*
  • Paraproteinemias / immunology
  • Polymerase Chain Reaction
  • Protein Sorting Signals / genetics
  • RNA, Messenger / analysis
  • Sequence Homology, Amino Acid

Substances

  • DNA Primers
  • Immunoglobulin A
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Protein Sorting Signals
  • RNA, Messenger

Associated data

  • GENBANK/S83559