PNPLA1 defects in patients with autosomal recessive congenital ichthyosis and KO mice sustain PNPLA1 irreplaceable function in epidermal omega-O-acylceramide synthesis and skin permeability barrier.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of monogenic genodermatoses that encompasses non-syndromic disorders of keratinization. The pathophysiology of ARCI has been linked to a disturbance in epidermal lipid metabolism that impaired the stratum corneum function, leading to permeability barrier defects. Functional characterization of some genes involved in ARCI contributed to the identification of molecular actors involved in epidermal lipid synthesis, transport or processing.

Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.

Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported.

Mice deficient for the epidermal dermokine β and γ isoforms display transient cornification defects.

Expression of the human dermokine gene (DMKN) leads to the production of four dermokine isoform families. The secreted α, β and γ isoforms have an epidermis-restricted expression pattern, with Dmkn β and γ being specifically expressed by the granular keratinocytes. The δ isoforms are intracellular and ubiquitous.

Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice.

Deimination, the conversion of protein-bound arginines into citrullines, is a post-translational modification catalyzed by a peptidylarginine deiminase (Pad). In the epidermis, three Pads are expressed, namely Pad1, 2 and 3, and the major deiminated protein is filaggrin. Deimination of fibrin has been observed in various pathological inflammatory conditions.

Corneodesmosin gene ablation induces lethal skin-barrier disruption and hair-follicle degeneration related to desmosome dysfunction.

Corneodesmosin (CDSN) is specific to desmosomes of epithelia undergoing cornification, mainly the epidermis and the inner root sheath of the hair follicles. CDSN nonsense mutations are associated with hypotrichosis simplex of the scalp, a rare disease that leads to complete baldness in young adults. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface.

Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection.

The main function of regulatory T lymphocytes is to keep autoimmune responses at bay. Accordingly, it has been firmly established that the repertoire of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) is enriched in autospecific cells. Differences in thymic-positive and/or -negative selection may account for selection of the qualitatively distinct regulatory and conventional T cell (Tconv) repertoires.

HLA-G unique promoter region: functional implications.

In contrast to the highly polymorphic HLA class Ia genes that exhibit a broad somatic tissue distribution, the restricted constitutive expression of HLA-G to trophoblast and a subset of thymic epithelial cells suggests tight transcriptional control of this MHC class Ib gene. Transactivation of MHC class I genes is mediated by three major regulatory modules present in their promoter region namely enhancer A, ISRE, and SXY. The 220-bp promoter sequence of HLA-G comprises modified enhancer A and SXY modules and lacks the ISRE which renders this gene unresponsive to NK-kappaB, IRF1, and class II transactivator DNA-binding factors.

The interchain disulfide bond between TCR alpha beta heterodimers on human T cells is not required for TCR-CD3 membrane expression and signal transduction.

In the present paper, it was attempted to define the amino acids or regions on TCR beta molecules that determine the TCR alpha-TCR beta interaction. Sequence studies on HBP-ALL variant cells with an intrinsic deficiency in TCR alpha beta dimer formation elucidated a conserved amino acid motif in the TCR-C beta beta-strand E, = Y(C)(L)(S)SRLR(V)(S)(A); this motif seems to represent one interaction area for the TCR alpha-TCR beta interaction. In addition, amino acids in the connecting peptide may be shaped in a precise structure (by the interactions with CD3 molecules?) involved in TCR alpha-TCR beta dimerization.

Defective interactions between TCR chains and CD3 heterodimers prevent membrane expression of TCR-alpha beta in human T cells.

The human TCR complex is composed of two clonotypic polypeptide chains, TCR-alpha and TCR-beta (or TCR-gamma and TCR-delta) associated with CD3 gamma-, delta-, and epsilon-chains and zeta 2 homodimers. All six polypeptide chains are indispensable for TCR membrane expression and signaling function. In the present paper is described the analysis of a new TCR membrane-negative Jurkat T cell variant: E6.

Abnormal T cell receptor V beta gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients.

Objective: The aim of this study was to assess T cell receptor V beta-gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients.

Methods: Cytometric analysis was performed on peripheral blood and synovial fluid lymphocytes from 12 patients using a restricted set of V beta-specific monoclonal antibodies (to V beta 5.1-3, V beta 6.

A highly conserved phenylalanine in the alpha, beta-T cell receptor (TCR) constant region determines the integrity of TCR/CD3 complexes.

In the present study, we have investigated the importance of a phenylalanine (phe195) in the Tcr-C alpha region on Tcr-alpha,beta/CD3 membrane expression. An exchange of phe195 with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with aspartic acid, histidine or valine prohibit completely Tcr/CD3 membrane expression. This seems to be due to a lack of interaction between mutated Tcr-alpha,beta/CD3-gamma epsilon,delta epsilon complexes and zeta 2 homodimers.

An alternative method for T-cell receptor repertoire analysis: clustering of human V-beta subfamilies selected in responses to staphylococcal enterotoxins B and E.

We have designed a convenient procedure for the analysis of V beta repertoire expression in polyclonal T-cell populations. In this procedure T-cell RNA is converted to cDNA, polydC-tailed with terminal deoxynucleotidyl transferase and submitted to one-side specificity PCR amplification with a constant region oligonucleotide primer. The amplified material is then analysed by reverse spot-test hybridization: after 32P-labelling, the amplification product is put to hybridize on a membrane where specially designed V beta subfamily-specific probes are immobilized.

Comparison of TCR-alpha beta sequences of cross-reactive anti-DR alloreactive T-cell clones: identification of possible contact residues based on charge complementarity between TCR chains and DR determinants.

We analysed alloreactive T-cell clones selected for their differential recognition of DR variants differing in the third hypervariable region (hvr) of the DRB1 gene (amino acid positions 67-70-71). This polymorphism leads to two main hvr3 types: a basic form (Leu67-Gln70-Arg/Lys71) and an acidic form (Ile67-Asp70-Glu71) where residue 70 is probably directly accessible to the TCR on DR beta chains. The TCRs have been sequenced.

Functional properties of HLA-DR-BON alleles associated with DQw5(w1) and with DQw7(w3): a family study.

Among the DR specificities undefined by serology, DR-BON is peculiar because RFLP cannot distinguish it from the well-defined allele DR1 even if the two specificities are very different functionally. The occurrence of two DR-BON-like alleles in the same family, one associated to the DQw5 split of DQw1 and the other associated to the DQw7 split of DQw3, enabled us to compare the properties of these alleles. The RFLP analysis showed a typical DR1-like picture for both alleles when probed with DR beta, but for one of the alleles the DQ beta probe gave a DQw7 pattern.

Evolution of the HLA-DR1 gene family. Structural and functional analysis of the new allele "DR-BON".

The molecules of the MHC are highly polymorphic and involve in Ag presentation; their striking genetic polymorphism allows probable interactions with a large variety of antigenic fragments when these are presented to the TCR. It is therefore of interest to explore the extent of this polymorphism and the mechanisms of its generation. We have studied the class II HLA-DR blank allele DR-BON that has been previously defined by MLR, restriction fragment length polymorphism, and two-dimensional gel electrophoresis.

Glutamate excretion triggering mechanism: a reinvestigation of the surfactant-induced modification of cell lipids.

Lipid alterations induced by surfactants to trigger glutamate excretion were investigated with an industrial strain of Corynebacterium glutamicum. The lipid composition of this strain was determined for cultures in a synthetic medium and in a complex medium. A distribution of complex lipids between the cell wall and the cell membrane is proposed.