Search PubMed⌕ Search

Biomedical subjects

J Dausset

Publications and source records attributed to J Dausset.

At least 109 records · Page 6Linked to original sources
PubMed1989

IgG rheumatoid factor in human and rabbit transplantation sera.

Sera of human recipients of kidney allografts and rabbit recipients of skin allografts were tested by means of enzyme immunoassays (EIA) for IgG rheumatoid factor (RF) combining with human IgG (RF-H) or rabbit IgG (RF-R). In humans, the mean OD value in EIA for RF-H was significantly higher in 185 sera of allograft recipients than in 46 pretransplantation sera and 100 sera of normal subjects. Furthermore, the mean OD in patients who rejected their grafts was higher than in patients with satisfactory graft function. Interestingly, there was no difference in OD values for RF-R between sera of graft recipients and sera of normal subjects. Of 52 rabbit recipients of skin allografts, 24 were positive for both RF-R and RF-H, 4 were positive only for RF-R, another 4 only for RF-H, and 20 were negative for both. Renal allografts originating from the previous donors of skin grafts resulted, in most instances, in a significant decrease in the strength of the reaction for both RF-R and RF-H. The possible role of graft rejection in stimulation of RF formation as well as the possible role of RF in graft rejection should be considered.

Animals↗
PubMed1989

[Increased risk of insulin-dependent diabetes for siblings of diabetic children with the DR 3 haplotype of the mother].

Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. Comparing the respective frequencies between affected and unaffected siblings, the relative risk was 8.1 (p less than 10(-6) among DR4p/DR3m positive siblings, but is was not significantly increased among DR3p/DR4m positive siblings. The excess of maternal DR3 among affected siblings of diabetic children could be due to a gestational event associated with HLA-DR3, e.g. education of the fetal immune repertoire or the transmission of a viral infection by the mother to the fetus during pregnancy, after reactivation of the latent viral disease.

Diabetes Mellitus, Type 1↗
PubMed1989

[Study of the HLA system and glyoxalase in 31 insulin-dependent diabetics free from micro and macro-angiopathies after more than a 20-year development].

Insulin-dependent diabetics are not equal as concerns vascular complications. Many factors have been incriminated. The object of this study was to determine if a genetic factor protected the insulin-dependent diabetic from vascular complications. The population included 31 unrelated, white insulin-dependent diabetic subjects (18 females and 13 males), with diabetes of over 20 years' duration (21 to 43 years, m +/- SD 27.82 +/- 6.03 years; age at diagnosis: 2 to 57 years, m +/- SD 22.7 +/- 15.19 years). The absence of vascular lesions was checked for by the following investigations: visual acuity, fundoscopic examination, retinal fluorescein angiography (Canon F 60 Z), systolic pressure on the thigh and ankle, Doppler velocimetry, plethysmography of the lower limbs, serum creatinine level, urinary protein. The study of the HLA A, B, DR specificities was carried out using the Tersaki microlymphocytotoxicity assay, those of C4 by high voltage gel electrophoresis followed by hemolytic detection, those of B1 using Alper's method and those of glyoxalase by gel electrophoresis followed by a glutathione redox reaction in order to test for a marker for a possible protective genetic factor against complications. The antigen frequencies found were compared with: 1) Those in the general Caucasian reference population (9th Histocompatibility Workshop, 1984). The study group presented the HLA characteristics known to occur in insulin-dependent diabetes: increase in A30, B8, B18, D6, DR3, DR4, BfF1 and decrease in A3, B7, DR2. Furthermore an increase in the frequency of DRw53, DQw2 and DQw3 alleles was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

The V gamma locus of the human T cell receptor gamma gene. Repertoire polymorphism of the first variable gene segment subgroup.

Southern blot analysis using a genomic probe of the human TCR-gamma chain first variable gene subgroup (V gamma I) was performed on DNA samples from both parents of 36 healthy Caucasian families. Two types of polymorphisms were found in these 72 unrelated DNA samples: three repertoire polymorphisms and two restriction fragment length polymorphisms (RFLP). In all cases, Mendelian inheritance of these polymorphisms was demonstrated. The most frequent repertoire polymorphism consists in the lack of the V gamma 4 and V gamma 5 segments. In 16% of chromosomes, the Eco RI and Taq I restriction fragments corresponding to V gamma 4 and V gamma 5 were lacking, with no additional bands. In these cases, a decrease of 10 kb was observed in the Bam HI fragment containing all V gamma I segments as compared with samples containing V gamma 4-V gamma 5 segments. To better understand this polymorphism, which takes place in a previously incompletely defined region, the central part of the V gamma I region, including the polymorphic V gamma 4-V gamma 5 segments, was cloned. This allowed us to localize precisely the V gamma 5 segment and thus complete the description of the V gamma I region. A striking homology of DNA and deduced amino acid sequences is present between V gamma 2 and V gamma 4 and between V gamma 3 and V gamma 5, much higher than that observed between V gamma 2 and V gamma 3 and between V gamma 4 and V gamma 5. The differences in nucleotide sequence occur mainly in the intron and three hypervariable regions. These results strongly suggest a gene duplication relationship between the segments V gamma 2-V gamma 3 and the segments V gamma 4-V gamma 5. The most frequent RFLP documented in this study is due to the combined absence of the Eco RI and the Taq I sites located in the noncoding region between V gamma 3 and V gamma 4. The haplotypic frequence of this RFLP is 6.9% of the general population. As the gamma/delta receptor may play an important role in immunological response, the biological relevance of the high degree of polymorphism occurring in the V gamma I region, as well as its possible association with some immune disturbances, should be further explored.

Amino Acid Sequence↗
PubMed1988

The required interaction between monocytes and peripheral blood T lymphocytes (T-PBL) upon activation via CD2 or CD3. Role of HLA class I molecules from accessory cells and the differential response of T-PBL subsets.

Previously, we have shown that paraformaldehyde-fixed monocytes are able to fully complement, in terms of [3H]dThd incorporation, a primary stimulus delivered to purified T cells by monoclonal antibodies (mAb) reacting with CD3 or CD2 molecules. Here, we show that depending on the stimulus used (CD3 mAb or different pairs of CD2 mAb) HLA class I molecules from monocytes are directly involved in complementary signals provided to T cells. This was evidenced by the following observations: (a) mAb reacting with the heavy or light chain of class I molecules, or their Fab fragments, completely blocked proliferation of peripheral blood lymphocytes (PBL) activated by CD3 mAb; (b) mAb against the heavy chain of HLA class I but not against beta 2-microglobulin partially blocked (approximately equal to 50%) PBL activation by the CD2 "GT2 + T111" mAb pair but did not block activation by CD2 "D66 + T111" mAb; (c) this pattern of inhibition was observed when anti-class I mAb were used in the soluble phase or when they were bound to monocytes subsequently fixed with paraformaldehyde and cultivated with purified autologous T cells; (d) fixed monocytes are able to restore interleukin (IL) 2 receptor expression on purified T cells stimulated by CD3 mAb or CD2 "GT2 + T111", contrary to anti-HLA class I mAb-pretreated monocytes. The inhibitory effects of anti-HLA class I mAb bound to monocytes were not found to be reversed by recombinant IL2 or recombinant IL1. We assume that HLA class I would be involved in two or more signals delivered to T cells by monocytes, the requirement in those signals depending on the initial stimulus applied to T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

HLA class I molecules are associated with CD1a heavy chains on normal human thymus cells.

The molecules encoded by the major histocompatibility complex play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. The function of the CD1 molecules, which are homologous to the major histocompatibility complex-encoded molecules but are encoded on human chromosome 1, is not known. HLA class I molecules and CD1a heavy chains share the ability to associate with several different cell-surface molecules. We show here, by several technical approaches, that HLA class I molecules are associated with CD1a heavy chains on the surface of normal thymus cells. The functional significance of this association during T-cell differentiation is discussed.

Antibodies, Monoclonal↗
PubMed1988

Use of a variable alpha region to create a functional T-cell receptor delta chain.

Two categories of T-cell antigen-specific receptor have been described. Most mature T lymphocytes have, on their membrane, an antigen receptor consisting of alpha and beta subunits, while early T cells and thymocytes possess a heterodimeric receptor termed gamma-delta. The DS6 clone, isolated from the peripheral blood of a patient with immunodeficiency, is a CD3+, CD4-, CD8- human T-cell line that expresses the disulfide-linked form of the gamma-delta antigen receptor. The nucleotide sequence analysis of DS6 cDNA makes clear that its variable region is a member of an alpha variable-region gene family. We have cloned and sequenced the germ-line joining and variable regions used to create the DS6 delta mRNA. Comparison of these sequences does not show evidence of extensive somatic mutations. The major difference between the germ-line and the T-cell antigen receptor delta cDNA sequence is an insertion of three consecutive nucleotides between the variable and joining segments and is evocative of somatic diversification rather than of the use of a germ-line-encoded diversity region.

Amino Acid Sequence↗
PubMed1988

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of HLA products encoded by the DR2 haplotypes of IDDM patients. The results show the following: (i) HLA-DQ molecules of HLA-DRw15-positive IDDM patients are different from those of HLA-DRw15-positive controls, suggesting that the HLA-DQ gene of DRw15 haplotypes is involved in a protective effect. (ii) HLA-DR and -DQ products of DRw16-positive IDDM are functionally indistinguishable from those of HLA-DRw16-positive controls. Furthermore, our data provide evidence that the residue at position 57 on the DQ beta chain could play a crucial biological role in antigen presentation to T cells as far as the DRw16 haplotype is concerned. This observation fits with the recent observation of correlation between DQ beta allelic polymorphism at position 57 and both susceptibility and resistance to IDDM.

Amino Acid Sequence↗
PubMed1988

Use of synthetic oligonucleotides for genomic DNA dot hybridization to split the DQw3 haplotype.

Comparison of two different HLA-DQ beta gene sequences from two DR4 individuals, probably corresponding to DQw3.2 (DQR4) and DQw3.1 (DQR5) specificities, has shown several nucleotide variations. Eight oligonucleotides (24 bases long), derived from these polymorphic areas, have been synthesized. Each oligonucleotide was hybridized to BamHI-digested DNA samples from eight families with HLA-DR4 individuals. Four polymorphic BamHI fragments were detected. Two of eight oligonucleotides gave a single signal (8.9 kilobases) on DQw3.2-positive haplotypes. We used one of these oligonucleotides in a genomic DNA dot hybridization and detected a hybridization signal only in DQw3.2-positive individuals. A very simple test like this allows the screening of a large population sample within a very short period.

Base Sequence↗
PubMed1987

Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations.

T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation. For comparison, polyclonal T cells from peripheral blood of healthy donors and blast cells from 19 cases of T lineage ALL were also studied. In this study we demonstrate the presence of a clonal rearrangement of the TRG gamma in 18 of the 22 B-lineage ALL cases and establish that this rearrangement, which generally involves the J gamma 1 region, is often monoallelic and appears different from the biallelic J gamma 2 rearrangement frequently seen in T-cell ALLs. In 9 of 22 cases, we found rearrangement of the genes of the TCR beta chain, which never involved the J beta 1 region. Conversely, the TRG gamma were seen in germline configuration in all 19 cases of B chronic lymphoid malignancies. In none of the 9 AML cases studied was TRG gamma and TCR beta chain gene rearrangement found. The TCR beta chain genes were rearranged in one B cell chronic lymphocytic leukemia (CLL). We also show that in B-lineage ALL, the cells probably use the same V gamma genes for TRG gamma rearrangements as the malignant cells in T-ALL and the polyclonal T cells. In none of the 13 B-lineage ALL cases investigated by Northern analysis was TCR beta mRNA expression detected, whereas a weak expression of TRG gamma transcripts was found in two of these cases. The correlations between surface phenotype, rearrangement of TRG gamma, TCR beta, and Ig H chain genes were analyzed. The significance of rearrangement of TRG gamma and TCR beta chain genes in B or pre-B cells is also discussed.

B-Lymphocytes↗
PubMed1987

Role in T-cell activation for HLA class I molecules from accessory cells: further distinction between activation signals delivered to T cells via CD2 and CD3 molecules.

The immunological function of major histocompatibility complex molecules, including HLA class I molecules, is to present antigens and/or their processed peptides to various lymphocyte subpopulations. Thus, they play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. We looked for a role of major histocompatibility complex molecules during T-cell activation induced by monoclonal antibody (mAb) or combinations of mAb recognizing the two well-characterized T-cell surface molecules CD3 and CD2. To activate T-cell peripheral blood lymphocytes, we used a CD3 mAb or two different pairs of CD2 mAb, CD2 "GT2 + T11(1)" and CD2 "D66 + T11(1)," which, as we have previously shown, deliver different signals of activation to T cells. Anti-HLA class I mAb blocked the activation induced by CD3 mAb or by CD2 GT2 + T11(1), but it did not block activation induced by CD2 D66 + T11(1). We observed this pattern of inhibition according to the stimulus used to activate T cells both when the anti-HLA class I mAbs were added to cultures of whole peripheral blood mononuclear cells and when they were fixed to monocytes only. In the latter case, purified monocytes were first incubated with the anti-HLA mAb (whether whole immunoglobulin or Fab fragment) and then fixed with paraformaldehyde before culture with autologous purified T cells. Anti-HLA class I fixed on monocytes prevented both interleukin 2 (IL-2) receptor expression and IL-2 synthesis on T cells. The inhibitory effects of anti-class I mAb bound to monocytes were not reversed by adding large amounts of recombinant IL-2 or recombinant IL-1, a finding consistent with the observations that accessory cells surface components can fully complement the signals directly delivered to T cells by CD2 or CD3 mAb. We conclude that HLA class I from accessory cells plays an important role in the early phase of T-cell activation when direct contacts between accessory cells and T cells are required.

Antibodies, Monoclonal↗
PubMed1987

Isolation of a human major histocompatibility complex class I gene encoding a nonubiquitous molecule expressed on activated lymphocytes.

The human major histocompatibility complex is a multigene family containing at least 20 class I genes. Included within this family are the loci encoding the highly polymorphic HLA-A, -B, and -C antigens present at the surface of most nucleated cells. The large number of genes detected with class I probes by Southern blot analysis and the existence of serological reagents defining nonubiquitous, non-HLA-A,B,C class I antigens suggest that products other than HLA-A,B,C antigens are encoded within the class I gene family. These products might be the human counterparts of the murine Qa and TL antigens. In order to identify non-HLA-A,B,C genes, we have developed a probe, JF11, located in noncoding regions flanking the HLA-A locus. This probe detects only a limited number of class I genes and does not detect HLA-A,B,C-associated restriction fragments on Southern blots. This probe was used to screen a human cosmid library. Some of the cosmids isolated with this probe were then transferred into mouse fibroblasts expressing human beta 2-microglobulin. One of the transfectants specifically reacts with one alloantiserum (HA2) that detects HLA class I molecules specific to HLA-A2-positive, phytohemagglutinin-activated T cells and not found on resting T or B cells. Data presented in this paper provide evidence for the isolation and expression of a class I gene encoding a nonubiquitous class I antigen that could be a human analogue of the murine Qa antigens.

Animals↗
PubMed1987

HLA and non-HLA phenotyping and genotyping in Austral and Gambier Polynesian Archipelagos.

Forty-one individuals from Rurutu Island (Austral Archipelagos) and 41 individuals from the Gambier Archipelagos have been typed for HLA; for blood groups ABO, Rh, MNSs, P, Kell, Kp, Lewis, Lutheran, Kidd; for the electrophoretic systems G6PD, 6-PGD, PGM1, PGM2, AcP, ADA, GPT, Est-D, GLO I, and for the immunoglobulin allotypes Gm and Km. There is a high degree of homogeneity among these Polynesian populations and among other Polynesian populations previously typed. However, small differences exist between the populations of the two archipelagos, possibly due to endogamy or to the smallness of the samples studied. A variant of HLA-Bw22 (called Bw22x) is described.

Blood Group Antigens↗