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J Dausset

Publications and source records attributed to J Dausset.

At least 145 records · Page 8Linked to original sources
PubMed1985

Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA.

We performed HLA genotyping by using restriction-enzyme fragments hybridized with specific HLA probes instead of traditional immunologic methods in two patients whose lymphocytes expressed so few HLA antigens on the cell surface that serologic methods failed. Segregation of restriction-fragment-length polymorphism permitted identification of the genotypes. In addition, known correlations between serologically determined antigens and restriction-fragment-length polymorphism were confirmed. We applied this approach in making therapeutic decisions regarding bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1985

Serological expression after sequential double transfection with purified HLA-A11 gene of mouse fibroblasts carrying human beta-2 microglobulin.

A genomic cosmid library constructed from DNA from a genotyped individual (JF = HLA-A11, Cw-, B38/A26, Cw7, B51) was screened for clones containing class I histocompatibility genes. Among these clones, one was found to carry a 4.8 kb Hind III fragment which is highly correlated with HLA-A11. This clone was used to transfect LMTK+ cultured mouse fibroblast transformants expressing human beta-2 microglobulin. The human beta-2 microglobulin heavy chain-associated determinant was positively detected by the M18 monoclonal antibody. HLA-A11 expression on these doubly transformed cells was specifically demonstrated by complement-dependent cytotoxicity with HLA-A11 + A3-specific but not with HLA-A3-specific monoclonal antibodies. Absorption studies with human alloantisera confirmed the presence on these cells of HLA-A11 determinants and of cross-reacting determinants which absorbed anti-HLA-A1 and -A3 alloantisera. The JF5-J27 transfected cell expressed both heavy and light chains of human class I histocompatibility genes.

Animals↗
PubMed1985

Relationship between postvaccinal anti-influenza antibodies, blood magnesium levels, and HLA antigens.

Seventy-eight healthy subjects belonging to 16 different families were submitted to an anti-influenza vaccination. The antibody titers and the red blood cell and plasma Mg concentrations were determined before and 30 days after vaccination. The population study performed on 32 subjects showed the occurrence of a higher antibody response (P less than 0.01) and a lower red blood cell Mg level, among the Bw35 individuals. These findings are confirmed by family studies: HLA identical sibs have values much closer to those of the propositi than to those of the HLA different sibs. The relationships between HLA, immune response, and Mg revealed by the present investigation are discussed in light of the literature together with the known associations between HLA Bw35 antigen and diseases.

Adult↗
PubMed1985

A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus.

DNA restriction fragments of the genes encoding HLA class II-beta antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), were analyzed: (i) A DR Taq I 12.7-kilobase-pair fragment might be a marker for the extended haplotype HLA-B8, DR3. (ii) In controls, DR4 haplotypes are associated with two distinct clusters of DQ restriction fragments (DQR4 and DQR5). Almost all (94%) DR4 patients belong to the DQR4 and not to the DQR5 cluster. This suggests that, among HLA-DR4 haplotypes, only DQR4 haplotypes are involved in susceptibility to insulin-dependent diabetes mellitus. (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 X 10(-4). However, these results must be interpreted with caution, taking into account the high number of statistical tests performed.

DNA Restriction Enzymes↗
PubMed1985

Exuberant restriction fragment length polymorphism associated with the DQ alpha-chain gene and the DX alpha-chain gene.

Cellular DNAs from individuals of 23 families were digested with five restriction endonucleases (Pvu II, EcoRI, HindIII, BamHI, and EcoRV) and then probed with a DX alpha-chain gene probe. Seventeen allogenotopes were observed, each of which could be assigned to a serologically defined haplotype by noting its segregation in families. Six sets of allogenotopes forming allelic series were noted. In comparison with restriction maps of the DQ alpha and the DX alpha regions, each of these series has been assigned to the DQ alpha or the DX alpha locus. Allogenotopes of the four DQ alpha series constitute three clusters correlating with the supertypic groups of class II histocompatibility antigens DQw1 (DR1, DR2, and DRw6), DRw53 (DR4, DR7, and DR9), and DR3 plus DR5 plus DR8. These 13 DQ alpha fragments constitute 22 different patterns. The two DX alpha series constitute two clusters, one of which is not found to be correlated strongly with DR specificities, whereas the other is correlated loosely (r = 0.45) with DR5 and DR7. This absence of strong linkage disequilibrium between the DX alpha series and the DR series contrasts with the DQ alpha series and suggests a recombination point between DQ alpha and DX alpha loci.

Alleles↗
PubMed1985

Phorbol ester induces a differential effect on the effector function of human allospecific cytotoxic T lymphocyte and natural killer clones.

Six-day allosensitized human peripheral blood lymphocytes treated for 12-18 hr with phorbol 12-myristate 13-acetate (PMA) were found to lose the capacity to kill the specific target in a standard cell-mediated lympholysis (CML) assay, but they were still effective in their ability to kill the tumor cell line K562. We investigated which antigens on the cell membrane involved in alloimmune recognition might be modified by PMA, since it was found that in a lectin-dependent CML assay, the lytic mechanism was not impaired. For this purpose, T3+, T4+ allospecific cytotoxic T lymphocyte (CTL) clones and either T3+ or T3- natural killer (NK) clones were generated from 6-day allostimulated lymphocytes. The results indicated that PMA inhibited the cytolytic function of both alloimmune CTL and NK T3+ clones. In contrast, PMA did not modify the effector cell function of T3- NK clones. Phenotypic analysis of T-cell surface antigens from T3+ clones showed that T3 molecule expression on the cell membrane was reduced by 80-90% after PMA treatment, whereas expression of both accessory T4 molecules, involved in antigen recognition, and receptor for interleukin 2 was increased. Moreover, the loss of function was transitory and could be restored 4 days after PMA treatment when the T3 molecules were fully reexpressed at the cell surface. Taken together, these data strongly suggest that (i) PMA prevents cell-mediated cytotoxicity by modulating the disulfide-linked heterodimer associated to T3 and described as the receptor for antigen on the cell surface of major histocompatibility complex (MHC) and non-MHC specific CTL clones, without affecting the lytic mechanism per se, and (ii) the expression of the receptor for the antigen present on the tumor cell line K562 is not decreased on T3- NK clones after PMA treatment and must be different from that on T3+ T-cell clones.

Antibodies, Monoclonal↗
PubMed1985

HLA and multiple sclerosis: population and families study.

Association between HLA and multiple sclerosis (MS) was investigated at the population level on 100 MS patients genotyped for HLA-A, B, C, DR and Bf, Glo, and on 155 patients phenotyped for the same HLA antigens. Association between MS and DR2 was clearly confirmed, although its strength is rather weak. No other genetic marker could be related to the disease, no haplotype nor any allelic combination could be recognized as MS specific, and antigen genotype frequencies among the diseased could not ascertain the mode of inheritance, although dominance is very likely. Computer analysis between HLA, Bf, Glo and age of the patient, sex, age of onset and evolution of MS, impairment indexes, titres of anti-DNA and anti-measles antibodies in CSF did not show any interaction. Twenty sib pairs and two trios of MS were also studied; they showed no significant distortion with the random distribution of haplotypes. DR2 gene frequency, however, was significantly higher in sib pairs showing one or two haplotypes than in HLA different affected siblings. Three crossing-overs were identified which suggest where the HLA-linked MS susceptibility (MSS) gene could be located within the HLA segment, while other epistatic MSS genes or environmental factors are likely to be important.

Female↗
PubMed1985

[Detection of polymorphism of HLA class II genes using synthetic oligonucleotides].

The recent sequence determination of exons of various HLA class II genes has allowed us to study the polymorphism of coding sequences of these genes on a sample of HLA-DR typed unrelated individuals. From this sequence determination have emerged polymorphic hypervariable areas. A 24-mer oligonucleotide has been synthetized, which corresponds to the first hypervariable region of the beta 1 domain of a DR-beta molecule. This oligonucleotide hybridized only with the DNA from DR3 or DR5 individuals tested, even under stringent conditions of washing. However, the existence of strong linkage disequilibrium among the 3 or 4 DR genes of the D region does not allow us to conclude that this sequence is epitope-specific.

Genes, MHC Class II↗
PubMed1984

Role of H-2 and non-H-2 genes in the control of blood magnesium levels.

Red blood cell (RBC) and plasma (P) magnesium levels have been determined in 372 male mice of 13 inbred and H-2 congenic strains with C3H or B10 genetic backgrounds. Several groups of individuals belonging to the same strains have been tested at various times over a 2-year period to verify the results. Time and interstrain variations are highly significant for both RBC and P Mg. Statistical analyses made either with or without corrections for the time effect show that the largest variations are due to the genetic background (P less than 10(-10) ), the effect of the H-2 complex being smaller but nevertheless highly significant (P less than 10(-4) to 10(-6) ), except for the RBC Mg of the strains with B10 background. These findings can be compared with those previously obtained in man, and they demonstrate the high heritability of blood Mg concentration and its association with the major histocompatibility complex or with closely linked genes.

Animals↗
PubMed1984

The heterogeneity and functional capacities of human thymocyte subpopulations.

Analysis of human thymocytes with monoclonal antibodies belonging to five distinct clusters of differentiation (CD1, CD3-CD5, CD8) revealed a high degree of phenotypic heterogeneity. Six subpopulations could be defined in the thymic compartment characterized by the presence of CD1 antigens (cortical type); four subpopulations could be defined in the compartment characterized by the lack of CD1 but by the presence of CD5 antigens (medullary type); two subpopulations could be defined in the compartment characterized by the lack of both CD1 and CD5 antigens. Thymic samples could be categorized as either high responder or low responder to phytohemagglutinin alone. The defect of low responders was, to a large extent, attributable to a lack of interleukin 2 availability in the medullary type compartment. Yet, cortical-type subpopulations, both from high and low responders, were able to respond to phytohemagglutinin alone to the same extent. Undesirable cell contamination was excluded by limiting dilution analysis. Moreover, cortical-type cells were found to be able to respond to concanavalin A alone, while medullary-type cells and total populations did not respond to concanavalin A alone. Thus, the human thymus includes a number of cell subpopulations involved in complex functional interactions.

Antibodies, Monoclonal↗
PubMed1984

Clusters of HLA class II beta restriction fragments describe allelic series.

Eighty-eight HLA haplotypes have been investigated for the presence or absence of 52 restriction fragments generated by four restriction enzymes (EcoRI, EcoRV, HindIII, BamHI), and detected by a DQ beta cDNA probe. Correlation analysis showed several sets of positively associated fragments forming 11 clusters. They constitute three different allelic series. The first coincides with DR alleles, the second with DQ alleles, and within the third, one cluster coincides with DRw53 (MT). As shown by comparative hybridization, most fragments belonging to the DR- as well as the DQ-related series correspond to DQ beta genes. In contrast, the MT-related series corresponds to DR beta genes. The evolutionary significance of these restriction fragment clusters is discussed.

Alleles↗
PubMed1984

Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis.

HLA-DR2 allele is negatively associated with insulin-dependent diabetes and positively associated with multiple sclerosis (MS). A 2.2-kilobase-pair EcoRI DNA restriction fragment detected with a beta-chain HLA-DC cDNA probe was found to be strongly correlated with HLA-DR2 in the normal population, but was absent in HLA-DR2 insulin-dependent diabetic patients. This fragment was found in HLA-DR2 multiple sclerosis patients with the same frequency as in controls. A beta-chain HLA-DC 12-kilobase-pair BamHI fragment might differentiate multiple sclerosis patients from healthy individuals.

DNA Restriction Enzymes↗