PubMed Health⌕ Search

Biomedical subjects

A Quesnel

Publications and source records attributed to A Quesnel.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and antigenic properties of reduced peptide bond analogues of an immunodominant epitope of the melanoma MART-1 protein.

Backbone modifications have been introduced into the melanoma derived peptide MART-1(27-35) to increase its binding to class I major histocompatibility complex HLA-A2 molecule, and ultimately to enhance its immunogenicity. Each analogue was obtained by replacing one peptide bond at a time in the natural epitope by the aminomethylene (CH2-NH) surrogate. All analogues displayed an increased resistance to proteolysis. Interestingly, the comparative results showed that five analogues bound more efficiently to HLA-A2 than the parent peptide. On the other hand, two pseudopeptide/HLA-A2 complexes were recognized by one melanoma-specific T cell clone. Close examination of the impact of such modifications at the molecular level provides useful supports for the rational design of stable compounds with applications in anti-tumour specific immunotherapy and in vaccine development.

Amino Acid Sequence↗
PubMed1999

Protection against lymphocytic choriomeningitis virus infection induced by a reduced peptide bond analogue of the H-2Db-restricted CD8(+) T cell epitope GP33.

Recent investigations have suggested that pseudopeptides containing modified peptide bonds might advantageously replace natural peptides in therapeutic strategies. We have generated eight reduced peptide bond Psi(CH2-NH) analogues corresponding to the H-2Db-restricted CD8(+) T cell epitope (called GP33) of the glycoprotein of the lymphocytic choriomeningitis virus. One of these pseudopeptides, containing a reduced peptide bond between residues 6 and 7 (Psi(6-7)), displayed very similar properties of binding to major histocompatibility complex (MHC) and recognition by T cell receptor transgenic T cells specific for GP33 when compared with the parent peptide. We assessed in vitro and in vivo the proteolytic resistance of GP33 and Psi(6-7) and analyzed its contribution to the priming properties of these peptides. The Psi(6-7) analogue exhibited a dramatically increased proteolytic resistance when compared with GP33, and we show for the first time that MHC-peptide complexes formed in vivo with a pseudopeptide display a sustained half-life compared with the complexes formed with the natural peptide. Furthermore, in contrast to immunizations with GP33, three injections of Psi(6-7) in saline induced significant antiviral protection in mice. The enhanced ability of Psi(6-7) to induce antiviral protection may result from the higher stability of the analogue and/or of the MHC-analogue complexes.

Amino Acid Sequence↗
PubMed1998

Is there IgA from gut mucosal origin in the serum of children with Henoch-Schönlein purpura?

Thirty-two children with Henoch-Schönlein purpura with or without renal symptoms were studied to characterize the IgA hyperglobulinemia observed in the serum of most patients. It was shown that only the IgA1 subclass concentration was increased. Secretory IgA and IgA to gliadin levels were frequently increased in serum, with a good correlation between them. Circulating IgA immune complexes were detected often and contained high activity to gliadin. In contrast, IgA activity to tetanus toxoid did not change. We failed to show any differences in renal involvement. These data suggest that elevation of serum IgA in Henoch-Schönlein purpura is due in part to a disturbance of the gut mucosal immune system, and the presence of circulating IgA immune complexes with dietary antigens can be postulated but cannot explain the occurrence of urinary symptoms.

Adolescent↗
PubMed1998

Incomplete trifluoroacetic acid deprotection of asparagine-trityl-protecting group in the vicinity of a reduced peptide bond.

During the Fmoc solid-phase synthesis of reduced peptide bond analogues, we observed that the trityl protection of an asparagine residue in the vicinity of a reduced peptide bond is not cleaved completely after the final trifluoroacetic acid deprotection step. The relative position of the Asn side-chain amine and of the aminomethylene bond as well as the preferential protonation of the secondary amine can be used to explain this phenomenon. We show that longer deprotection times or the use of methyl-trityl protection partially improves the yield of the Asn-deprotected peptide whereas xanthenyl protection totally overcomes this problem.

Antigens, Viral↗
PubMed1998

Focal symmetrical encephalomalacia in a 6-month-old Dorset sheep.

Neurological examination of a sheep that had acute onset of recumbency and mental depression indicated a diffuse symmetrical thalamocortical lesion. Cerebrospinal fluid analysis suggested a degenerative central nervous system disease. Thiamin administration resulted in partial and temporary improvement. Brain histological lesions were typical of focal symmetrical encephalomalacia.

Animals↗
PubMed1997

Comparative analysis of methods for collection and measurement of immunoglobulins in cervical and vaginal secretions of women.

The purpose of this study was to systematically compare 3 collection methods, Sno-strips, wicks and cervical-vaginal lavage, for analysis of immunoglobulin concentrations in female genital secretions. In each of 8 women, absorbent wicks and Sno-strips were applied at 4 locations: the lateral wall of the vagina; the posterior vaginal fornix; the surface of the exocervix; and the endocervical canal. Cervical-vaginal lavage was then performed in 4 women with 5 ml PBS. Immunoglobulin and protein concentrations in lavage samples were generally over 100 times lower than in the secretions captured directly from mucosal surfaces with either Sno-strips or wicks. Capture of undiluted secretions with either wicks or Sno-strips allowed calculation of actual immunoglobulin concentrations at specific mucosal sites: for example, median IgA levels were consistently highest in the endocervix and lowest in the vagina. Such information may be crucial in evaluating the correlates of protective immunity against micro-organisms that infect or invade discrete regions of the genital mucosa.

Adolescent↗
PubMed1997

Humoral immune response within the lung in HIV-1 infection.

In order to study the humoral immune defences in the respiratory tract during HIV-1 infection, we measured the levels, local productions and anti-HIV and antibacterial activities of IgG and IgA in the bronchoalveolar lavage fluid (BALF) and serum of 61 adult patients with severe HIV infection and of 56 HIV- controls. Albumin was used as the serum transudation factor. The increase of immunoglobulin levels in the serum of HIV-infected patients was confirmed. The IgG level was also increased in epithelial lining fluid (ELF), whereas the total IgA level was unchanged and secretory IgA (SIgA) level was decreased. The ELF/serum immunoglobulin ratios suggested that the IgG present in ELF resulted mainly from transudation, in contrast to SIgA, which was synthesized locally in controls but greatly diminished in HIV-infected patients. IgG to HIV-1 could be detected in BALF of all the patients, but IgA to HIV-1 only in 30% of patients. BAL IgG reacted more consistently and with a broader array of HIV-1 antigens than did IgA. BAL IgA, when present in samples, reacted primarily with viral envelope antigens. Because IgA specificities to some HIV-1 antigens were detected more intensively by BAL than by serum immunoglobulins, we conclude that the mucosal immune response is distinct from that in serum. IgG antibody activity to Streptococcus pneumoniae was decreased in HIV-infected patients' sera, and IgA antibody activities to S. pneumoniae and to Pseudomonas aeruginosa were decreased in ELF in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Quantification of IgA and IgG and specificities of antibodies to viral proteins in parotid saliva at different stages of HIV-1 infection.

Paired sera and parotid saliva from 75 HIV-1-infected patients, divided in three equal groups with CD4+ cell counts > 500, 200-500 and < 200/mm3, respectively, were analysed for IgG, IgA and secretory IgA (sIgA) concentrations and for IgG and IgA antibody directed to HIV-1. Twenty-nine age-matched HIV-subjects were used as controls. In serum the concentrations of immunoglobulins were significantly increased in HIV-infected subjects compared with controls, and a progressive increase of IgA and sIgA was noticed while the CD4+ cell count decreased. In contrast, concentrations of IgA and sIgA were not different in parotid saliva between the four subject groups. By an ELISA test directed towards HIV-1 proteins, 73 of the 75 serum specimens from the HIV-infected subjects (97%) and 43 of the corresponding saliva (57%) were found positive for specific IgA antibodies to HIV-1, with an even distribution among the three groups of patients. By Western blotting multiple specificities of IgA to HIV-1 proteins were not frequently found in patients. By contrast, in spite of an IgG concentration in saliva about 100 times lower than that of IgA, reactivities were significantly higher for IgG than for IgA antibodies, especially to env and to pol HIV-1 products. Altogether, these data suggest that the regulation of IgA production in HIV-infected subjects is independent in serum and in parotid saliva. This imbalance of IgA/IgG antibodies to HIV-1 at the mucosal level appears to be a specific feature of HIV-1 infection, and may raise important issues in terms of local protection after immunization.

Adolescent↗
PubMed1996

Efficient binding to the MHC class I K(d) molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif.

Peptides eluted from the MHC class I K(d) molecule are generally nonamers that display a strong preference for Tyr in position 2 and Ile or Leu in position 9. We investigated the binding ability of several synthetic peptides which did not fit this consensus motif. In our peptides, Tyr(2) was substituted by other amino acids, i.e. LeU, Ile or Met. These peptides were variants of the 252-260 K(d)-restricted peptide SYIPSAEKI derived from the Plasmodium berghei circumsporozoite protein. They bound to purified K(d) molecules in vitro with intermediate affinity. One of them was tested for in vivo stimulation of T cells and induced a cytotoxic response. These results demonstrate the importance of binding motif refinement to discover new binding characteristics and new ligands such as low-affinity peptides.

Amino Acid Sequence↗
PubMed1995

Purification of synthetic peptide libraries by affinity chromatography using the avidin-biotin system.

The specific interaction between biotin and avidin was exploited in the affinity purification of solid-phase synthesized peptide libraries. During peptide library synthesis, by means of the single-resin method in which coupling on variable positions is carried out using an equimolar mixture of amino acids, biotin was used to cap the unreacted amino groups remaining after coupling of the equimolar amino acid mixture. The following synthesis and deprotection procedures were performed as usual in tert,-butyloxycarbonyl chemistry. The purification of the peptide mixture containing N-biotinylated sequences was performed by affinity chromatography on an avidin-agarose column. The unwanted terminated sequences were retained in the avidin column while the purified peptide mixture was eluted as indicated by reverse-phase HPLC and MS analysis monitoring. The avidin column was regenerated and the biotinylated sequences were released under reversible denaturing conditions. The usefulness of biotinylation for peptide library purification is demonstrated here for the first time for a peptide mixture containing by-products that cannot be separated from the mixture by classical HPLC purification. This purification technique could be applied to all syntheses, presenting difficult reacting steps.

Amino Acid Sequence↗
PubMed1994

Early impairment of gut mucosal immunity in HIV-1-infected children.

This study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.

CD4-Positive T-Lymphocytes↗
PubMed1994

Is there IgA of gut mucosal origin in the serum of HIV1 infected patients?

This study was performed in 77 HIV1 seropositive adult patients to characterise the IgA hyperglobulinaemia seen in the serum during the course of HIV infection. It was shown that both IgA1 and IgA2 subclass concentrations were simultaneously increased but the IgA1 increase was predominant. Secretory IgA (SIgA) concentration was significantly increased and IgA activity to gliadin, bovine serum albumin, and casein could be detected and was correlated with SIgA concentration. In contrast, IgA activity to cytomegalovirus and to tetanus toxoid did not correlate with total IgA concentration. These data suggest the presence of IgA from gut mucosal origin in the serum of these patients. Hyper IgA was inversely correlated with the CD4+ cell number. The increase of all parameters studied varied according to the total IgA concentration in the serum but was also directly related to the stage of immune deficiency in patients with hyper IgA.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Prognostic value of serum immunoglobulin A antibodies to pol gene products during HIV-1 infection.

Serum specimens from 66 HIV-1-infected subjects were tested by ELISA for the presence of IgA antibodies to HIV-1: 44 samples were found positive and 37 were confirmed by immunoblot. In these subjects, the presence of anti-HIV IgA antibodies was studied in relation to the total count of circulating CD4+ lymphocytes and to the level of serum IgA. A significative correlation (P < 0.03) was found between the absence of IgA to the subunit p68 of the reverse transcriptase and a count of CD4+ cell < 400/mm3 or total IgA level over 4.25 g/l. The same pattern was observed for the IgA antibodies to the p52 subunit but the association was just not significant (P < 0.07). No significant decrease was noted for the IgA directed towards the other proteins of HIV-1, especially the products of the gag gene.

Adult↗
PubMed1992

Antibodies to Epstein-Barr virus and cytomegalovirus in relation to CD4 cell number in human immunodeficiency virus 1 infection.

Interaction between herpesviruses and human immunodeficiency virus (HIV)1 is postulated in the progression of HIV disease. In order to evaluate the specific antibody responses directed to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and to provide serological evidence suggesting reactivation of these viruses able to accelerate the immunodeficiency, we studied IgA and IgG titres to EBV and CMV in the serum of HIV positive patients in relation to the CD4 cell number. The titres of IgG antibodies to EBV and the prevalence of IgG to CMV were significantly higher in HIV positive patients compared to control high risk HIV negative subjects. In HIV infected patients, anti-VCA IgG antibodies increased and anti-EBNA IgG antibodies decreased progressively in relation to the decline of CD4 cell number whereas anti-CMV IgG antibodies did not varied significantly at the same time. Anti-VCA IgA and anti-EA IgG antibodies were found uncommonly and with low titres. IgA antibodies to EA and CMV were not detected in any patient. The variations in EBV antibody response that we describe in HIV infection were previously reported in other immunodeficiency states and could be distinctive of these diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[The plural family in a rural African environment. An example of plantation economy: the Dayes plateau in Southwest Togo].

"Study of the transition to a plantation economy in populations on the Dayes plateau (SW Togo) shows the progressively preponderant role of the domestic group. Responsibility for production, for continuity of the labour force and for the demographic continuity of groups which used to be held by lineal authorities is now exercised at [the] domestic unit level. Although this results in greater autonomy for women, it also results in radical changes in the marriage rate. The loss of control of lineal structures over marriages appears to have led to increasing conjugal instability to link in particular with the number of unmarried couples. The authors carry out a comparative study of autochthonous groups (Ahlon and Ewe) and an immigrant group (Kabye) and study the consequences of this situation with regard to both demography and family structures. They show that autochthonous and immigrant groups are interdependent in the forming of demographic structures and report that there are many family models, essentially in the autochthonous population." (SUMMARY IN ENG)

Africa↗