Amino acid sequence of λ chain of human immunoglobulin A

Okada, Yoshimi; Nozu, Yuzo; Titani, Koiti; Watanabe, Shinichiro; Hara, Hiromichi; Kitagawa, Masayoshi

doi:10.1016/0019-2791(72)90040-7

Cited by 11 publications

(2 citation statements)

References 9 publications

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“…Three different isotypic variants, designated Oz (5), Kern (6), and Mcg (7), are characterized by site-specific sequence substitutions and the CA genes encoding these sequences have been identified (2). In addition, 10 other sequence variations in CA have been recognized among monoclonal light chains (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), but the genetic basis for these differences is not known.…”

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Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Frangione¹,

Moloshok²,

Prelli³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Serologic, structural, and genetic analyses have shown that the constant (C) region of human Kc light chains is encoded by a single gene, whereas that of K chains is encoded by multiple genes. We have determined the complete C region amino acid sequence of two (J), and constant (C), widely separated in germ-line DNA. The V gene encodes the first 95-100 residues of the VL, and the J gene encodes the remaining 13 residues. In the course of B-cell development, gene segments V and J are joined together and eventually linked to the CL-encoding gene segment C. Despite these similarities, the chromosomal location, number, and order of K and X chain-encoding gene segments are strikingly different. Human K chains, for example, are the products of tandemly arranged V, J, and C gene segments located on chromosome 2 (1). During somatic differentiation, one each of multiple germ-line VK and JK genes is joined together; the selected V/J gene is eventually spliced to a single CK gene (1). In contrast, the V, J, and C genes encoding X chains are located on chromosome 22 and differ from their K counterparts by the presence of at least six CA genes (2); furthermore, the CA genes are in tandem and, in the mouse (3), are each preceded by a J gene segment.Polymorphism among human CA genes was first evidenced through serological and sequence analyses of monoclonal A light chains and, more recently, has been demonstrated at the genomic level (2, 4). Three different isotypic variants, designated Oz (5), Kern (6), and Mcg (7), are characterized by site-specific sequence substitutions and the CA genes encoding these sequences have been identified (2). In addition, 10 other sequence variations in CA have been recognized among monoclonal light chains (8-18), but the genetic basis for these differences is not known.In the course of determining the complete amino acid sequence of two monoclonal human XVI amyloid-associated MATERIALS AND METHODSProtein Isolation and Purification. Bence Jones proteins Mor and Sut were isolated from urine specimens by zone electrophoresis on polyvinyl chloride blocks (Pevikon; Kemanord, Sweden) and were further purified by gel filtration through agarose/polyacrylamide gel columns (Ultrogel AcA54, LKB) as described (20). The purity and molecular weights of the proteins were determined by NaDodSO4/ polyacrylamide gel electrophoresis with or without 0.1 M 2-mercaptoethanol (21) and by immunoelectrophoresis using antisera to light chain and normal human sera.Complete Reduction and Radioalkylation. Proteins Mor and Sut were reduced in 6 M guanidine/0.6 M Tris HCl/1 mM EDTA, pH 8.2, containing 5 mM dithiothreitol for 1 hr at 370C and were alkylated by the addition of iodo[14C]acetic acid (0.7 mCi/mmol; 1 Ci = 37 GBq; Amersham) to a final concentration of 11 mM (22). After incubation for 1 hr at 23°C, the samples were desalted by passage through Sephadex G25 fine (Pharmacia) columns equilibrated in 1 M acetic acid and then lyophilized.Peptide Preparation. Trypsin and staphylococcal protease V8 (23) were us...

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mentioning

confidence: 99%

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Frangione¹,

Moloshok²,

Prelli³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…Several additional substitutions have been described (8)(9)(10)(11)(12)(13)(14)(15)(16)), but it is unknown whether these represent allelic variants or distinct isotypes. The human immunoglobulin X light chain genes have been mapped to chromosome 22 (17) at band q1l (18,19), and six nonallelic X C region genes (CxJ to Cx6) have been characterized on a 40-kilobase (kb) stretch of DNA (20).…”

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Human immunoglobulin C lambda 6 gene encodes the Kern+Oz-lambda chain and C lambda 4 and C lambda 5 are pseudogenes.

Dariavach¹,

Lefranc²,

Lefranc³

1987

Proc. Natl. Acad. Sci. U.S.A.

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Six nonallelic immunoglobulin A constant region genes have been previously characterized on a 40-kilobase stretch of DNA. The nucleotide sequences of the three upstream genes of this cluster (Cj1, Cx2, Ck3) have been determined by other workers and shown to encode, respectively, the isotypic Mcg, Kern-Oz-, and Kern-Oz+ constant region of the A chains. In this paper, we report the sequence of the three downstream genes of this cluster and show that two of them (CA4 and Cx5) are pseudogenes. However, Ck6 encodes a Kern+Oz-chain and corresponds to the fourth isotype described among the A proteins sequenced so far. A potentially active J4 (oining) segment, with the canonical heptamer and nonamer sequences for rearrangement, is located 1.5 kilobases upstream of Cx6. The amino acid sequence encoded by the Cx6 gene is compared with the constant region sequences of various monoclonal Bence Jones A proteins. Allotypic and isotypic differences confirm the polymorphism and complexity of the human Ck locus.In humans, the constant (C) region of the immunoglobulin X light chains consists of at least four nonallelic or isotypic forms that differ by limited amino acid substitutions to produce the serological markers Kern (Ke) (1, 2), Oz (3-5), and Mcg (6, 7). Several additional substitutions have been described (8-16), but it is unknown whether these represent allelic variants or distinct isotypes. The human immunoglobulin X light chain genes have been mapped to chromosome 22 (17) at band q1l (18,19), and six nonallelic X C region genes (CxJ to Cx6) have been characterized on a 40-kilobase (kb) stretch of DNA (20). The number of CA genes varies between six and nine per haploid genome (21). These variations were detected by restriction fragment length polymorphism (21) and seem to have arisen from unequal meiotic crossing-over with a duplication of the CA2 and CA3 genes. Moreover, three additional CA-like genes have been recently identified, which map on different stretches of DNA and are nonallelic (22). One of these is a pseudogene, whereas the two others encode a putative A chain C region whose sequence differs from that of the X chains described so far.Only three QC genes (CA1, Cx2, and CA3) belonging to the cluster described by Hieter have been sequenced (20), and they have been shown to encode, respectively, the Mcg, Ke-Oz-, and Ke-Oz+ C region of the A chains. In this paper, we report the sequences* of the three genes located downstream in this cluster and show that two of them (CA4 and CA5) are pseudogenes, whereas CA6 encodes a Ke+Oz-chain, the fourth isotype described among the proteins sequenced so far. This CK6 gene has a potentially active JX6 joining region, with the canonical heptamer and nonamer sequences for rearrangement, 1.5 kb upstream of the coding C region. MATERIALS AND METHODSConstruction of a Phage Library from LY67 DNA. DNA prepared from LY67 cells (a X-producing Burkitt's lymphoma) (23)

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Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups

et al. 1990

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Comparison of 60 human immunoglobulin variable lambda (IGLV) sequences allowed us to define seven subgroups designated V lambda I to V lambda VII. We demonstrate that all lambda proteins sequenced so far fall into the subgroups I, II, III and VI, and that the lambda regions previously assigned to subgroups IV and V belong, in fact, to subgroups III and II, respectively. Four sequences not belonging to any of the subgroups I, II, III and VI define the new subgroups IV, V and VII. Interestingly, these subgroups show a higher homology to rabbit or mouse V lambda genes than to the other human V lambda subgroups. By comparison of the proteins either with the sequences deduced from the germ-line genes or with the consensus sequences, the rate of amino acid changes due to somatic mutations or allelic variations was evaluated in several lambda proteins. Framework and complementarity-determining regions of the human IGLV genes and proteins were delineated. Alignment of the lambda sequences shows that functional V-J rearrangement occurs, with or without deletion of nucleotides encoding one or two amino acids at the 3' end of the V gene. Diversity of the third complementarity-determining region is due to somatic mutations and to flexible V-J junction, but there is no evidence of N-diversity in the human lambda locus.

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Amino acid sequence of λ chain of human immunoglobulin A

Cited by 11 publications

References 9 publications

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Human immunoglobulin C lambda 6 gene encodes the Kern+Oz-lambda chain and C lambda 4 and C lambda 5 are pseudogenes.

Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups

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