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Biomedical subjects

J M Claverie

Publications and source records attributed to J M Claverie.

At least 19 recordsLinked to original sources
PubMed1992

Antibodies and reactive T cells against the malaria heat-shock protein Pf72/Hsp70-1 and derived peptides in individuals continuously exposed to Plasmodium falciparum.

Pf72/Hsp70-1, a heat-shock protein of m.w. 72 kDa from Plasmodium falciparum is one of the Ag of interest to be included in a polyvalent vaccine against malaria. It is one of the major immunogens present in a fraction of purified blood stage parasites that elicited protection against experimental infection of Saimiri monkeys with blood stages of P. falciparum. It is present at all blood stages and one of its B cell epitopes is also detected on the surface of the infected hepatocyte. Moreover, Pf72 appears to be well conserved among different isolates of P. falciparum. We have examined the immune response against Pf72/Hsp70-1 in individuals from different age groups living in a holoendemic area (West Africa). The immune response against the native Ag (purified from schizonts and called Pf/Hsp70) was analyzed both at the humoral level by ELISA and at the cellular level by assessing in vitro proliferation and IFN-gamma production of PBMC. Of the individuals studied 52% had a statistically significant level of anti-Pf/Hsp70 antibodies as compared with unexposed individuals. These positive individuals showed a heterogeneous distribution because significant levels of antibodies were found in 70% of the adults but in only 26% of the children. The presence of Pf/Hsp70-specific reactive T cells in the blood was detected in 32% of the individuals. The total anti-Pf/Hsp70 antibody level (IgG+IgM) appeared strongly age related and correlated positively with parasite exposure, whereas the T cell response failed to correlate either with the antibody level or with age. Moreover, PBMC of donors responded to the Pf/Hsp70 in a dissociated way, namely, by either T cell proliferation or IFN-gamma production. Ten synthetic peptides based on sequences found in the C-terminal part of Pf72/Hsp70-1 were further tested as potential T cell epitopes. The proliferative response of PBMC from individuals continuously exposed to the parasite showed that three peptides more frequently trigger significant T cell proliferation (in 21% to 27% of the individuals) and three others less frequently (10%). None of these peptides allowed detection of reactive T cells in PBMC of Europeans with no previous exposure to malaria. Some of the stimulating peptides are highly similar to human heat-shock Hsc and Hsp70 with large stretches of identical amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Identifying coding exons by similarity search: alu-derived and other potentially misleading protein sequences.

The search for significant local similarities with known protein sequences is a powerful method for interpreting anonymous cDNA sequences or locating coding exons within genomic DNA sequences at a stage where the average contig size is still very small. The BLASTx program, implemented on the National Center for Biotechnology Information server, allows a sensitive search of all putative translations of a nucleotide query sequence against all known proteins in a matter of seconds. From an analysis of the current databases, I report a set of protein sequences exhibiting high local similarity to Alu repeat or vector sequences. These entries can lead to misleading interpretations of similarity searches. During the course of this study, the protease of a human spumaretrovirus was found to have integrated the 3' end half of the U2 snRNA.

Amino Acid Sequence↗
PubMed1991

Random association between the peptide repertoire of A2.1 class I and several different DR class II molecules.

The interaction between synthetic peptides and A2.1 class I MHC molecules has been investigated using an inhibition of Ag presentation assay and unbiased peptide sets derived of either viral or eucaryotic origin. For the various sets, strong binding (defined as significant inhibition at the 30 micrograms/ml level) was detected in 7 to 46% of the peptides tested, with an overall frequency of 26%. A set of self-peptides derived from human beta 2 microglobulin was also included in the study. In this case, strong binding was detected in 3 of 15 peptides (20%), thus formally demonstrating a lack of self-/non-self-discrimination at the level of class I molecules. When the whole A2.1-binding database of 105 peptides thus generated was examined by sequence analysis, a significant correlation was found with a recently proposed A2.1-binding motif, whereas no particular positive or negative association was detected between the capacity to bind A2.1 and three different class II alleles (DR1, DR5, and DR7). Finally, using this approach, several peptides capable of binding both A2.1 and multiple DR alleles have been identified, suggesting possible candidates for development of peptide vaccines eliciting both class I and class II restricted responses.

Amino Acid Sequence↗
PubMed1991

The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules.

Kallmann syndrome associates hypogonadotropic hypogonadism and anosmia and is probably due to a defect in the embryonic migration of olfactory and GnRH-synthesizing neurons. The Kallmann gene had been localized to Xp22.3. In this study 67 kb of genomic DNA, corresponding to a deletion interval containing at least part of the Kallmann gene, were sequenced. Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids. This candidate gene (ADMLX) is interrupted in its 3' coding region in the Kallmann patient, in which the proximal end of the KAL deletion interval was previously defined. A 5' end deletion was detected in another Kallmann patient. The predicted protein sequence shows homologies with the fibronectin type III repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration.

Amino Acid Sequence↗
PubMed1991

Identification of a major human immunodeficiency virus-1 reverse transcriptase epitope recognized by mouse CD4+ T lymphocytes.

Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.

Animals↗
PubMed1991

A strong propensity toward loop formation characterizes the expressed reading frames of the D segments at the Ig H and T cell receptor loci.

A compilation of murine and human Ig H and TcR beta D segment sequences was used to estimate the relative usage of the various reading frames and to look for associated sequence patterns. We confirm a strong bias in the expression of the Ig H D segments, with more than 90% (murine) and 85% (human) expressed peptides resulting from a preferred reading frame. Remarkably, 86% (mouse) and 90% (human) of those peptides contain at least one glycine residue. All but one of the atypical preferred D peptides contain serine or proline residues and are found in the immediate vicinity of glycine residues provided by specific JH segments. The presence of tyrosine residues is also a characteristic feature of expressed reading frames in both mouse (75%) and human (90%). These results suggest that the constraints of forming a flexible loop within the third complementarity-determining region, is a factor in the preference for a particular reading frame in Ig H D. For the TcR beta D segments, glycine is specified in most reading frames, and no significant preference is observed.

Amino Acid Sequence↗
PubMed1991

Biased amino acid distributions in regions of the T cell receptors and MHC molecules potentially involved in their association.

We have analysed, in the context of the available structural information, the frequency of occurrence of different amino acids in functional regions of both the class I MHC antigens and of the TCR alpha and beta chains. We found that in class I MHC molecules, charged residues are found frequently among those which are presumably dedicated to interactions with the TCR, while the aromatic side chain residues are found more in the interior of the groove. In the TCR, the Asn residue appears with high frequency in all the CDR equivalents. The TCR CDR3s of both alpha and beta chains are particularly rich in Gly, whereas the CDR1 and CDR2 loops exhibit strong biases in favour of charged residues. Accordingly, the interactions between the MHC molecule and the peptide antigen appear to be essentially mediated by hydrophobic interactions and hydrogen bonding, while electrostatic interactions between charged residues might be important in the association of TCR and MHC molecules. The observation that each CDR1 and CDR2 is biased towards a particular set of amino acids, taken together with the nature of the protruding residues on the MHC helices, allows us to propose, in the frame of a molecular model of the MHC-TCR complex, several plausible configurations.

Amino Acid Sequence↗
PubMed1991

WOBB.C: a portable software package for defining and searching ambiguous sequence patterns.

WOBB.C is a set of C-written programs designed to build and manipulate ambiguous sequence patterns and to locate them within collections of protein or nucleotide sequences. The search module involves the perceptron algorithm introduced by Stormo et al. (1982) [Nucleic Acids Res 10:2997-3011] in the context of biosequence analysis. The originality of WOBB.C resides in its portability and in a flexible interface, allowing the definition of patterns in three different ways: automatically, from a multi-alignment; interactively, from a character string, or from an explicit text file script.

Amino Acid Sequence↗
PubMed1990

Structure of the ecdysone-inducible P1 gene of Drosophila melanogaster.

The P1 gene codes for a major RNA, which accumulates specifically in the fat body cells at the late third larval stage of Drosophila melanogaster development under the positive control of the insect molting hormone 20-hydroxyecdysone. The primary structure of the P1 gene and the 5' upstream flanking region to position -776 relative to the transcription start was determined by sequence analysis of a cloned genomic DNA segment and two cDNAs containing sequences complementary to the 5' and 3' ends of the P1 transcript. The RNA coding region spans 3469 nucleotides and contains a 59-base-pair intron close to its 5' end, as predicted by computer analysis and established by S1 nuclease protection, primer extension and cDNA sequencing. The predicted P1 polypeptide contains 1030 amino acids, including a putative 16-amino acid signal peptide and two stretches of 12 and 11 aspartic and asparagine residues. Short stretches of nucleotide sequences similar to sequences located in the 5' regions of other genes expressed in the D. melanogaster fat body were found in the proximal promoter and transcribed region of the P1 gene.

Amino Acid Sequence↗
PubMed1990

Protein instruction.

Explore the source record for details and available documents.

Histocompatibility Antigens Class I↗
PubMed1989

Conformational analysis of T immunogenic peptides by circular dichroism spectroscopy.

The structure of two T-immunogenic peptides, one from the gag p24 protein of the human immunodeficiency virus, the other from the 11.1 gene product of Plasmodium falciparum, was studied by circular dichroism spectroscopy in various pH and solvent conditions. Although both sequences are predicted to adopt an alpha-helical conformation and one of them is a repeat of a perfect alpha-amphipathic sequence pattern, these two peptides exhibit a strong propensity to adopt an extended, turn or aperiodical conformation in solution.

Circular Dichroism↗
PubMed1989

Implications of a Fab-like structure for the T-cell receptor.

The antigen-specific receptor of T lymphocytes (TCR) and the Fab moiety of immunoglobulins are expected to fold into similar three-dimensional structures because of their identical protein domain organization, the conservation of key residues and their overall sequence homology. However, T cells mostly appear to recognize short peptide antigens bound to MHC class I or class II presenting molecules. A complete model of the human leucocyte antigen molecule (HLA-A2) reconstructed from the alpha-carbon coordinates was used to investigate the putative organization of a TCR/peptide/HLA-A2 complex. In this article, Jean-Michel Claverie and co-workers show that the respective geometries of a Fab-like TCR structure and of the HLA-A2 antigen binding site suggest a model where the third variable regions of both chains of the TCR mainly interact with the peptide antigen, while the first and/or second less variable regions are in position for making contact with residues pointing up from the alpha 1 and alpha 2 helical regions of the HLA-A2 molecule.

Amino Acid Sequence↗
PubMed1989

Extensive structural homology between H-2 K/D/L antigens and non-polymorphic class I Qa, Tla and "37" molecules suggests they may act as peptide carriers.

Key structural features of H-2 K/D/L and HLA A/B/C class I molecules were identified by analysing the available sequences with reference to the 3-D structure of HLA-A2. Most of them were found to be conserved in a panel of 6 Qa and 4 Tla sequences. This finding, in addition to the high overall sequence similarity between polymorphic and non-polymorphic class I molecules strongly suggests a possible role for the latter in peptide binding, transport and/or presentation.

Amino Acid Sequence↗