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Jean-Pierre Bouvet

Publications and source records attributed to Jean-Pierre Bouvet.

5 recordsLinked to original sources
PubMed2004

Somatic mutations can lead to a loss of superantigenic and polyreactive binding.

Although antibodies have been assumed to bind a specific antigen, evidence exists showing that a single antibody can bind to multiple unrelated antigens. We previously studied a human monoclonal antibody expressing a mutated form of the V(H)3-73 gene and displaying anti-tubulin activity in a patient suffering from an immunocytic lymphoma. Despite its expression of a V(H)3 family member, this immunoglobulin failed to react with protein A (SpA), suggesting that somatic mutations could account for its change in specificity. To examine this possibility, we produced recombinant Ig expressing germ-line (IgM kappa-Germ) or the mutated form (IgM kappa-PER) of the V(H)3-73 fragment. Comparison of the respective affinities of the two Ig demonstrated that IgM kappa-Germ restores its SpA-binding capacity, and shows a moderate decrease in its affinity for tubulin. Interestingly, IgM kappa-Germ displayed polyreactive specificity for different autoantigens, which contrasted to the monospecific binding of IgM kappa-PER to tubulin. These results suggest that the monoreactive IgM kappa-PER antibody may be derived from a natural polyreactive antibody through somatic mutation. In addition, both temperature modification and mild denaturation succeeded in recovering the polyreactivity of IgM kappa-PER, which favors the view that conformational modifications of the tertiary structure of antibodies may play a key role in the genesis of polyreactivity.

Amino Acid Sequence↗
PubMed2003

Impairment by mucosal adjuvants and cross-reactivity with variant peptides of the mucosal immunity induced by injection of the fusion peptide PADRE-ELDKWA.

Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.

Adjuvants, Immunologic↗
PubMed2003

Protein Fv produced during viral hepatitis is an endogenous immunoglobulin superantigen activating human heart mast cells.

Protein Fv, an endogenous protein produced in the liver, is released in biological fluids during viral hepatitis. Acute and chronic viral hepatitis can be associated with cardiovascular derangements. Protein Fv induced the release of histamine, tryptase and the de novo synthesis of prostaglandin D(2) and cysteinyl leukotriene C(4) from mast cells isolated from human heart tissue (HHMC). Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion. The maximal percent histamine secretion induced by protein Fv correlated (r(s) = 0.60; p < 0.05) with that induced by anti-IgE, whereas there was no correlation between the release caused by proteins Fv and C5a. Preincubation of HHMC with protein Fv or anti-IgE caused complete cross-desensitization to subsequent challenge with heterologous stimulus. HHMC from which IgE had been dissociated no longer released histamine in response to anti-IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv-induced release. Three human monoclonal IgM V(H)3(+) inhibited protein-Fv-induced secretion of histamine from HHMC, whereas monoclonal IgM V(H)6(+) did not inhibit the release induced by protein Fv. Protein Fv acts as an endogenous immunoglobulin superantigen by interacting with the V(H)3 domain of IgE to induce the release of mediators from HHMC.

Adult↗
PubMed1997

Vaginal pH neutralization by semen as a cofactor of HIV transmission.

OBJECTIVE: To explain the high frequency of heterosexual transmission of AIDS in subSaharan countries, by investigating post-intercourse semen retention in the vagina for local pH neutralization as a possible interference factor with acidic inactivation of HIV virions. METHODS: Two semen markers, prostate-specific antigen and prostatic acid phosphatase, were measured and compared with the pH values in the vaginal washes of 69 women from the Central African Republic. The capacity of semen to raise the vaginal pH was also investigated in vitro. RESULTS: Of 61 non-menstrual specimens, 74% contained at least one semen marker. The specimens with high levels of markers (group I) displayed an almost neutral pH (median 6.1), at variance with the semen-free group II (median: 3.7, P<0.003), and with group III (median: 4.0) corresponding to low or past semen retention. The in vitro study confirmed the high neutralization capacity of semen. CONCLUSIONS: It is expected that post-intercourse neutralization of pH will both favor male-to-female transmission and prevent the acidity-associated loss of infectivity of the female-derived virions, thus allowing female-to-male transmission during further sexual contact.

Journal Article↗