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Biomedical subjects

P Dariavach

Publications and source records attributed to P Dariavach.

11 recordsLinked to original sources

The B-cell antigen receptor of the five immunoglobulin classes.

Several proteins associate with surface IgM to form the antigen receptor. We show that just two, the alpha and beta associated chains, are sufficient to reconstitute an IgM surface receptor in fibroblasts. Contrary to expectation, a common alpha chain associates with all five immunoglobulin classes. We propose that B-cell antigen receptors consist of a common alpha/beta heterodimer associated with each immunoglobulin class. But the classes differ both in the glycosylation of their associated alpha chain and in their dependence on alpha/beta for surface transport.

Amino Acid Sequence

The mouse IgH 3'-enhancer.

A lymphoid-specific transcription enhancer element has recently been identified at the far 3' end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350-bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C alpha 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3'-enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage-specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3'-enhancer (in addition to the intron-enhancer) on mu gene expression plasmids effected a small increase in mu mRNA levels in stable plasmacytoma transfectants.

Animals

The promoter regions of the T-cell receptor V9 gamma (TRGV9) and V2 delta (TRDV2) genes display short direct repeats but no TATA box.

T lymphocytes expressing the T-cell gamma delta receptor have been shown to express preferentially the T-cell receptor V9 gamma (TRGV9) gene, in association with the T-cell receptor V2 delta (TRDV2) gene. In this paper, we report that the promoter regions of the TRDV2 and TRGV9 genes, which are preferentially expressed early in T-cell differentiation, display short direct repeats but no TATA box, in contrast to the V gamma genes belonging to subgroup I. The TCCTCAGT octanucleotide found 100 pb upstream of the ATG of the HD-Mar V alpha transcript, a TCR V alpha gene without a TATA box, is observed upstream of TRDV2 but not TRGV9. Of interest is the presence of a characteristic decanucleotide AGGTGGT(T)GAG in the promoter regions of both the TRDV2 and TRGV9 genes.

Base Sequence

Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions.

In the human T cell receptor gamma (TRG) locus, fourteen variable (TRGV) genes belonging to four subgroups have been identified upstream of two constant region (TRGC) genes. Three joining segments, JP1, JP and J1, have been localized upstream of TRGC1, and two others, JP2 and J2, upstream of TRGC2. In this report, we demonstrate that a unique Xho I fragment of 120 kilobases (kb) contains the fourteen TRGV genes and that the hybridization of that fragment in pulsed-field gel electrophoresis (PFGE) allows linkage of the variable region to the constant region locus. We also show that the variable and the constant regions are remarkably close to each other since the distance between V11, the most 3' V gamma gene, and JP1, the most 5' J gamma segment, is only 16 kb. With its 14 V gamma genes, spanning 100 kb, the two C gamma genes and 5 joining segments covering less than 40 kb and only 16 kb separating the most 3' V gene from the most 5' J segment, the human TRG locus spans 160 kb of genomic DNA and represents a particularly condensed locus compared to the other rearranging gene loci.

Amino Acid Sequence

Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains.

The mouse CTLA-4 gene has been shown to code for an activated lymphocyte-associated sequence belonging to the Ig gene superfamily. We now report on the molecular cloning and study of the human corresponding gene isolated from a genomic library and designated Hu-CTLA-4. The Hu-CTLA-4 gene exists as a single copy per human haploid genome and maps to band q33 of chromosome 2. It comprises 3 exons notwithstanding the leader sequence. The first exon encodes a V-like domain of 116 amino acids, the second one a hydrophobic putative transmembrane region of 37 amino acids and the third one a 34 amino acid putative cytoplasmic domain. Whereas the overall homology between the human and murine CTLA-4 proteins is 76%, there is, remarkably, a complete identity of their cytoplasmic domains. This complete interspecies conservation comes in support of an important role for this domain in CTLA-4 function.

Amino Acid Sequence

Variable region genes in the human T-cell rearranging gamma (TRG) locus: V-J junction and homology with the mouse genes.

The locus of the human T cell rearranging gamma (TRG) or T cell receptor gamma chain genes comprises at least 14 variable genes (TRGV) belonging to four subgroups, five joining segments (TRGJ) and two constant region genes (TRGC). Nine V gamma genes belong to subgroup I, whereas subgroups II, III and IV each consists of a single gene respectively designated V9, V10 and V11. T cells expressing the gamma chain (TRG+) and recognized by the anti-Ti gamma A monoclonal antibody have been shown to rearrange the V9 gene. In order to assess the N diversity at the V-J junction in the TRG+ cells, the germline sequences of the segments involved in the V-J rearrangements must be known. In this paper, we report the sequences of the germline V9 and V10 genes. Comparison of the V-J junction and N region from transcripts or rearranged TRG genes belonging to the different subgroups shows no evidence of D segments in the human TRG locus. Sequences of the rearranged V11 gene from the JM cell line and those of the VA and VB pseudogenes, located upstream of V9 and V11 respectively, are given. Our results bring the number of human V gamma genes whose sequence is known to 13 and reveal unexpected homology with the mouse V gamma genes.

Amino Acid Sequence

Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia.

Polymorphism of immunoglobulin lambda constant region (IGLC) genes has been studied in French, Lebanese and Tunisian people. The human IGLC polymorphisms appear as EcoRI restriction fragment length variations-8, 13, 18 or 23 kb-, these polymorphic fragments being related to a number of IGLC genes varying from six to nine per haploid genome. DNAs digested with the endonucleases EcoRI and HindIII were hybridized to a human IGLC probe and an immunoglobulin lambda intervening sequence region probe containing the J lambda 2 gene segment. Restriction fragments detected in Southern hybridizations were assigned to the IGLC locus map. Family studies allowed us to confirm the allelic nature of four of the different EcoRI restriction fragments observed. Frequencies of the corresponding alleles in French, Lebanese and Tunisian populations were determined and compared. The decrease of the 8-kb fragment (allele A1) frequency and, conversely, the increase of that of the 13-kb and 18-kb fragments (alleles A2 and A3) seemed to be correlated to a Negroid African contribution in the gene pool more important in Tunisia than in Lebanon.

Deoxyribonuclease EcoRI

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

Six nonallelic immunoglobulin lambda 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 (C lambda 1, C lambda 2, C lambda 3) have been determined by other workers and shown to encode, respectively, the isotypic Mcg, Kern-Oz-, and Kern-Oz+ constant region of the lambda chains. In this paper, we report the sequence of the three downstream genes of this cluster and show that two of them (C lambda 4 and C lambda 5) are pseudogenes. However, C lambda 6 encodes a Kern+Oz- chain and corresponds to the fourth isotype described among the lambda proteins sequenced so far. A potentially active J lambda (joining) segment, with the canonical heptamer and nonamer sequences for rearrangement, is located 1.5 kilobases upstream of C lambda 6. The amino acid sequence encoded by the C lambda 6 gene is compared with the constant region sequences of various monoclonal Bence Jones lambda proteins. Allotypic and isotypic differences confirm the polymorphism and complexity of the human C lambda locus.

Amino Acid Sequence