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P Pellet

Publications and source records attributed to P Pellet.

9 recordsLinked to original sources
PubMed1996

Allelic repertoire of the human MHC class I MICA gene.

The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular alpha1, alpha2, and alpha3 domains of the MICA gene from twenty HLA homozygous typing cell lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions. Thus, the total number of MICA alleles is sixteen. Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.

Alleles↗
PubMed1991

Heterogeneity of the breakpoint localization in malignant cells with a 9p11 chromosomal abnormality.

The p11 band of the short arm of chromosome 9 is involved in various cytogenetic alterations occurring in several malignant diseases. Using probes isolated from the 9p11 band in the study of a case of alpha-heavy-chain disease (MAL) with t(9;14)(p11;q32), we studied the DNA from seven malignant cell samples, including four cases of acute lymphoblastic leukemia with tdic(9;12)(p11;p12). Using pulsed-field electrophoresis analysis we demonstrated that the breakpoints were 3-300 kb distant from the original MAL breakpoint without clustering within the subset of leukemias with the tdic(9;12).

Chromosome Aberrations↗
PubMed1990

Alpha heavy chain disease of patient MAL: structure of the non-functional rearranged alpha gene translocated on chromosome 9.

Alpha heavy chain diseases (HCD) are lymphoproliferative disorders characterized by the production of truncated alpha immunoglobulin heavy chain without associated light chains, alpha HCD MAL is featured by multiple structural alterations of the alpha 1 productive gene and on original t(9;14)(p11;q32) translocation involving the other rearranged alpha 1 allele. We present here the structure of the der(9) chromosome. Sequence analysis provides evidence that the translocation occurred after local pairing of the two chromosomes mediated by an almost perfect nonameric sequence, followed by a staggered double-strand break of chromosome 14. This translocation occurred on a V(D)J rearranged locus; unexpectedly, there were a deletion of the 3' part of the VH gene, several insertions of non-immunoglobulin-related genes and multiple mutations, i.e. alterations reminiscent of those occurring on the HCD productive genes.

B-Lymphocytes↗
PubMed1989

The productive gene for alpha-H chain disease protein MAL is highly modified by insertion-deletion processes.

alpha-H chain diseases (HCD) is a human lymphoproliferative disorder, characterized by the production of truncated alpha-Ig H chains, without associated L chains. In this study, we have analysed the serum protein, the alpha-HCD mRNA and the rearranged alpha-HCD gene from the leukemic cells of a patient (MAL) with alpha-HCD. The abnormal MAL serum Ig consisted of short alpha 1-chains, lacking VH and CH1 domains (only CH2 and CH3 domains were present). The alpha-HCD mRNA (1.2 kb) was shorter than a normal alpha-mRNA (2 kb); the corresponding cDNA had sequences for the leader, a 84-bp sequence of unknown origin and the CH2 and CH3 exons. The establishment of the sequence of the productive alpha-HCD MAL allele revealed two major deletions; that of the VH region as well as that of the CH1 region. The JH region is altered by multiple mutations, small insertions and a duplication of the psi JH3 region. A large insert (INS1), of 360 bp (containing the 84 bp exon found in the cDNA), replaces the deleted VH region. INS1 is non-Ig related and apparently of nongenomic origin. A large second insert (509 bp), is located between the enhancer and the switch region. Insert2 contains repetitive non-Ig-related sequences and a small Ig-related sequence. All these alterations resulted in an abnormal mRNA, which comprises the leader, a 84-bp alien exon derived from INS1 and the CH2 and CH3 exons of the alpha 1-gene.

Amino Acid Sequence↗
PubMed1989

Molecular analysis of a t(9;14)(p11;q32) translocation occurring in a case of human alpha heavy chain disease.

We performed the cloning and sequencing of the der(14) breakpoint of a new chromosomal translocation involving the 14q32 immunoglobulin locus. This t(9;14)(p11;q32) translocation was found in a case of malignant lymphoma occurring in human alpha heavy chain disease. A rearranged alpha 1 gene fragment was cloned and shown to contain chromosome 9 information by Southern blotting on sorted chromosomes and by in situ hybridization. Sequence analysis of the junction point region established that the breakage occurred 3' to the heavy chain joining region. In contrast to the data obtained in other translocations affecting 14q32 immunoglobulin locus, the recombination did not involve the immunoglobulin heavy chain locus specific recombination signals on chromosome 14, or homologous sequences on chromosome 9. In the present case, the existence of two almost perfect inverted repeats flanking the junction point suggests that the translocation originated from a local pairing of the two chromosomes 9 and 14. Chromosome 9 fragments sequenced in the vicinity of the breakpoint did not share significant homology with sequences listed in GenBank and EMBL data bases.

Base Sequence↗
PubMedDate not supplied

MIC genes in non-human primates.

MIC molecules belong to the immunoglobulin superfamily, are encoded within the MHC region and are recognized by gamma/delta T-cell receptors. In humans, at least two functional genes (MIC-A* and MIC-B*) and two pseudogenes (MIC-C* and MIC-D*) exist. Functional MIC gene copies are characterized by a high degree of polymorphism, while pseudogenes bear several debilitating mutations either in the putative extracellular region or in the transmembrane region of the molecule. In this study we sequenced these segments of MIC genes in seven non-human primates in order to determine whether debilitating mutations were present. All the MIC primate genes studied were highly homologous to their human counterparts, and cystein residues involved in the maintenance of the immunoglobulin-like structure were highly conserved. Furthermore, none of the MIC genes studied contained stop codons in the extracellular or transmembrane segments of the molecule, which suggests that at least one functional gene copy exists in non-human primates. A distinct family of MHC immunoglobulin-like genes was recently identified within the MHC class I region in humans (Bahram et al., 1994; Leelayuwat et al., 1994). Members of this MIC (MHC class I chain related) gene family belong to the immunoglobulin superfamily. Similar to classical class I MHC genes, they are characterized by three distinct extracellular domains (alpha 1-3), a transmembrane (TM) segment and a cytoplasmic segment, each encoded by a separate exon (Bahram et al., 1994; Bahram et al., 1996). Other similarities between MIC genes and classical MHC genes include a high degree of polymorphism (Fodil et al., 1996; Pellet et al., 1997) and recognition by T-cell receptors (Groh et al., 1998). These findings suggest that the putative MIC-A* chain has evolved for a function that is related to, but quite distinct from, that of typical MHC class I chains.

Amino Acid Sequence↗