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F Kourilsky

Publications and source records attributed to F Kourilsky.

11 recordsLinked to original sources
PubMed1991

Surface CD4 density remains constant on lymphocytes of HIV-infected patients in the progression of disease.

In an attempt to question the influence of circulating virus, soluble gp120 or CD4 self-reacting antibodies upon results of CD4+ T-cell immunophenotyping in AIDS patients, five anti-CD4 mAb defining several epitopes of the V1 and V2 domains of the CD4 molecule were used to analyse the epitopic density of CD4 on lymphocytes of seropositive patients taken at stages II, III and IV of HIV infection, according to the Centers for Disease Control (CDC, Atlanta) classification. Our results demonstrate that each CD4 epitopic density measured on circulating lymphocytes remains constant at a mean level of 46,000 epitopes per cell whatever the stage of the disease and whatever the serum p25 concentration. These data provide evidence that antibody accessibility to several CD4 epitopes is not altered by putative interactions between CD4 molecules and circulating virus, soluble gp120 or anti-CD4 autoantibodies. If such binding events, as expected, do occur in vivo, they are of too low a magnitude to influence the immunophenotyping. Furthermore, we show that mAb specific for different epitopes in the V1 and V2 domains of the CD4 molecule can be used interchangeably for the biological followup of the CD4+ cell population in blood samples of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Characterization of monoclonal antibodies directed against distinct conserved epitopes of human immunodeficiency virus type 1 core proteins.

Two mouse hybridoma cell lines secreting antibodies to the Human Immunodeficiency Virus (HIV) p25 major core protein and its precursors p55 and p41, were developed after immunization with the highly cytopathic Zaïrian HIV-1 isolate, NDK. These monoclonal antibodies also react with the gag gene products from HIV-1-BRU prototype and present cross reaction with HIV-2-ROD, and SIV-AGM. They map into topographically distinct areas of p25 and define epitopic regions topographically separated from those recognized by four other anti-p25 mAb suggesting the existence of at least 6 spatially distinct epitopic regions on HIV-1-p25 core protein.

Animals↗
PubMed1990

An early postinfection signal mediated by monoclonal anti-beta 2 microglobulin antibody is responsible for delayed production of human immunodeficiency virus type 1 in peripheral blood mononuclear cells.

We recently found (C. Devaux, J. Boucraut, G. Poirier, P. Corbeau, F. Rey, M. Benkirane, B. Perarneau, F. Kourilsky, and J.C. Chermann, submitted for publication) a latency in the human immunodeficiency virus (HIV) type 1 cytopathic effect in the human T-cell lymphotropic virus type I immortalized T-cell line MT4 that was mediated by anti-beta 2 microglobulin (beta 2m) monoclonal antibodies (MAb). Here we describe a delay in viral particle production in peripheral blood mononuclear cells (PBMC) that was mediated by three (B1-1G6, B2-62-2, and HC11-151-1) of four anti-beta 2m MAb tested, the nonefficient MAb (C21-48A) being specific for an epitope on beta 2m that was masked by association with the human leukocyte antigen class I heavy chain. Experiments were designed to determine the mechanism of interference. PBMC incubated with anti-beta 2m MAb before viral exposure were not protected from HIV infection. In addition, anti-beta 2m MAb were not efficient in preventing syncytium formation between HIV-infected PBMC and CD4-positive MT4 cells. In contrast, anti-beta 2m MAb treatment of freshly infected PBMC significantly delayed HIV production in these cells. The window of cell sensitivity to anti-beta 2m MAb treatment took place during a very early post-HIV-binding stage. The possible mechanism of anti-beta 2m MAb action is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1985

HLA class I genes: from structure to expression, serology and function.

HLA class I genes have been isolated from phage and cosmid libraries and assayed by transfection into murine L cells. The transfection step proved to be very important because of the large number of genes (and pseudogenes) in this family. All functional genes characterized so far in this way are "classical" class I genes, i.e. members of the HLA-A, -B or -C families. Three of these have been sequenced (HLA-A3, -Aw24; HLA-Cw3) in addition to the pHLA 12.4 pseudogene. Sequence comparisons indicate, in particular, extreme conservation of the 3' non-coding region between allelic HLA-A locus genes; the general organization of all these genes (8 exons) is very similar. Restriction mapping around the functional genes has been performed to investigate the degree of conservation (e.g. between HLA-A3 regions from 2 different individuals) and examine allelism at the DNA level (e.g. between HLA-A3 and HLA-Aw24 regions). Exon shuffling experiments followed by serological analysis of the expressed product indicate that, as expected, specificities are determined by the first two domains of the molecule. However, further constructs show that as soon as a single exon is exchanged most specific reactivities disappear. CTL analysis of murine cells expressing HLA molecules has run into many difficulties but still holds promise for the study of structure-function relationships in this system.

Alleles↗
PubMed1983

Specificity of monoclonal antibodies against human thyroglobulin; comparison with autoimmune antibodies.

Ten monoclonal antibodies (mAb) directed against human thyroglobulin (hTgb) were produced, purified and characterized. The mAb avidity for hTgb ranged from 10(-10) to 10(-6) M. The species specificity of the mAb was as follows: eight mAb reacted with monkey Tgb, three with dog Tgb and one with pig Tgb; none with bovine and ovine Tgb. The binding of mAb to hTgb was not significantly inhibited in the presence of Tgb carbohydrate moieties, tyrosine, iodotyrosines and iodothyronines. The topology of the antigenic determinants recognized by the 10 mAb on hTgb was explored by inhibition of Tgb binding of radiolabeled mAb by the other antibodies. Six distinct clusters of reactivity were described. Localization of the antigenic determinants recognized by mAb on hTgb was attempted using tryptic fragments of hTgb to inhibit the binding of mAb to hTgb. The inhibitory effect of hydrolysis products was different for each mAb but exhibited partial analogies between mAb of the same cluster of reactivity. Anti-hTgb autoimmune antibodies (aAb) purified from sera of Graves patients cross-reacted essentially with mAb of one out of the six clusters. These results demonstrate that the large number of antigenic determinants presented by the hTgb are not disseminated on the molecule but are clustered in antigenic regions. Furthermore, from the six antigenic regions evidenced in this paper, only one is involved in autoimmune antibody production in Grave's disease.

Animals↗
PubMed1980

Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A.

Many applications envisioned for liposomes in cell biology and chemotherapy require their direction to specific cellular targets. The ability to use antibody as a means of conferring specificity to liposomes would markedly increase their usefulness. We report here a method for covalently coupling soluble proteins, including monoclonal antibody and Staphylococcus aureus protein A (ref. 4), to small sonicated liposomes, by using the heterobifunctional cross-linking reagent N-hydroxysuccinimidyl 3-(2-pyridyldithio)propionate (SPDP, Pharmacia). Liposomes bearing covalently coupled mouse monoclonal antibody against human beta 2-microglobulin [antibody B1.1G6 (IgG2a, kappa) (B. Malissen et al., in preparation)] bound specifically to human, but not to mouse cells. Liposomes bearing protein A became bound to human cells previously incubated with the B1.1G6 antibody, but not to cells incubated without antibody. The coupling method results in efficient binding of protein to the liposomes without aggregation and without denaturation of the coupled ligand; at least 60% of liposomes bound functional protein. Further, liposomes did not leak encapsulated carboxyfluorescein (CF) as a consequence of the reaction.

Animals↗
PubMedDate not supplied

Anti-beta 2-microglobulin monoclonal antibodies mediate a delay in HIV1 cytopathic effect on MT4 cells.

We attempted to select monoclonal antibodies (mAb) which reacted with T-cell surface molecules and were able to interfere with the human immunodeficiency virus type 1 (HIV1) replicative cycle in the MT4 T-leukaemic cell line. In comparison with OKT4A, an anti-CD4 mAb, only one mAb, HC11.151.1, was found to significantly delay HIV-induced cytopathic effect on MT4 cells among the 15 mAb tested which reacted with MT4 cell surface antigens. Biochemical and immunological characterization of HC11.151.1 demonstrated its specificity for beta 2-microglobulin (beta 2m), the light chain of human leukocyte antigen (HLA) class I molecules. Other beta 2m-specific mAb were tested in order to assess whether this effect represented an intrinsic capacity of HC11.151.1 or whether it was a common feature shared by all anti-beta 2m mAb. Three (B1.1G6, B2.62.2 and BBM1) of the four anti-beta 2m mAb demonstrated the same protective effect, whereas C21.48A, which was devoid of a functional effect, was directed towards a beta 2m epitope involved in binding to the HLA class I heavy chain molecule. The physiological relevance of this observation is discussed.

Antibodies, Monoclonal↗