The human intraepithelial lymphocyte marker HML-1 is an integrin consisting of a beta 7 subunit associated with a distinctive alpha chain.
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Amino Acid Sequence↗
Biomedical subjects
T Meo
Publications and source records attributed to T Meo.
The mouse mammary tumour virus long terminal repeat encodes a type II transmembrane glycoprotein.
Superantigens are products of bacterial or viral origin which stimulate large numbers of T cells as a consequence of the interaction of particular V beta chains of the T cell receptor with class II major histocompatibility complex (MHC) molecules and superantigen on the stimulating cell. The Minor lymphocyte stimulatory (Mls) antigens, originally discovered as strong lymphocyte stimulatory determinants in vitro and subsequently shown to delete T cells expressing specific V beta chains during development, have recently been shown to be genetically linked to endogenous mouse mammary tumour viruses (MTVs). This stimulation is effectuated by an unidentified product encoded by an open reading frame (orf) present in the 3' long terminal repeat (LTR) of MTVs. Using in vitro translation in the presence of rough microsomal vesicles, we show that (i) the orf of MTV encodes a type II transmembrane glycoprotein (N-terminus intracellular, C-terminus extracytoplasmic), and (ii) a cotranslationally secreted orf protein is not produced. We have also isolated and sequenced several endogenous MTV orfs (MTV-1, MTV-6 and MTV-13) which are involved in the deletion of V beta-bearing T cells; each of these sequences are nearly identical to each other. These observations, together with sequence comparisons of several orf genes, lead to a model of action of viral superantigens.
Amino Acid Sequence↗
Recombinational biases in the rearranged C1-inhibitor genes of hereditary angioedema patients.
DNA structural changes responsible for hereditary angioedema were sought in the C1-inhibitor gene, which contains unusually dense clusters of Alu repeats in various orientations. Among patients belonging to 45 unrelated families, eight partial C1-inhibitor gene deletions and a partial duplication were found. Four deletions had one of the boundaries within the gene and the other in extragenic regions--in three cases 5' of the gene and in one case 3' of the gene. The boundaries of the partial duplication and of the remaining four deletions mapped instead within a few kilobases of exon 4. The same element--Alu 1--the first of three tandem Alu repeats preceding exon 4, contained one of the breakpoints of each of these five rearrangements. Moreover, these recombination breakpoints spread over the entire length of Alu 1, in contrast with the tight clustering observed near the 5' end of Alu sequences rearranged in other human genes. Thus, two uncommon recombinational biases are observed in the Alu rearrangements of hereditary angioedema patients; one promotes the occurrence of intragenic breakpoints in a single Alu repeat, and the other allows the breaks to be distributed over the entire Alu structure rather than within the hot spot of the left Alu monomer. A region of potential Z-DNA structure, located 1.7 kb upstream of Alu 1, may contribute to both peculiarities.
Angioedema↗
Role of Ia-like products of the main histocompatibility complex in conditioning skin allograft survival in man.
This report correlates the survival time of 93 intrafamilial skin allografts performed under conditions of main histocompatibility complex (HLA) haploidentity with donor-recipient compatibility for products of the HLA-A, -B, -C, and -DR, as well as C3 proactivator, Glyoxalase I, and P loci located on the human 6th chromosome. Incompatibilities for HLA-A and -B (and to a lesser extent for HLA-C) and(or) for HLA-DR products exerted a strong influence upon the fate of skin allografts. When HLA-A and -B were considered alone, the most compatible group of grafts had a mean survival time of 15.8 d, as compared with 11.3 d for the most incompatible transplants. HLA-DR compatibility alone was associated with a mean survival time of 15.3 d, whereas HLA-DR-incompatible grafts had a mean survival time of 11.5 d. Incompatibilities for C3 proactivator, Glyoxalase I, and P did not have a significant effect upon graft survival. There was no evidence of an association between donor-recipient incompatibility at HLA-A, -B, or -C or at HLA-DR; such incompatibilities occurred independently of each other, in spite of the state of linkage disequilibrium known to exist between HLA-B and -DR. Incompatibilities for HLA-A, -B, and for HLA-DR exerted a potent additive effect upon graft survival. Skin grafts bearing one, two, or three incompatibilities had a mean survival time of 16.2, 13.7, and 10.7 d, respectively (P <0.0005).The results point to the important role played by the Ia-like products of the HLA complex (HLA-DR) in conditioning skin allograft survival in man. This consideration may be of direct relevance to the potential clinical usefulness of in vitro serological techniques for the detection of donor-recipient compatibility for HLA-DR.
Female↗
C2 deficiency and a lupus erythematosus-like illness: family re-evaluation.
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Adult↗
Assignment of genes for immunoglobulin kappa and heavy chains to chromosomes 6 and 12 in mouse.
Using somatic cell hybrids from fusions of lymphocytes of two different mouse stocks with the myeloma cell line X63-Ag8, we have assigned genes for the immunoglobulin heavy and kappa-type light chains to chromosomes 12 and 6, respectively. The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations. In the hybrid cells these metacentric chromosomes can be distinguished from the acrocentric chromosomes of myeloma origin, permitting correlation of Ig chain expression with mitotic loss of individual metacentric chromosomes.
Animals↗
A haplotype study of HLA complex with special reference to the HLA-DR series and to Bf. C2 and glyoxalase I polymorphisms.
Fifty-three French families were typed for alleles at seven loci of the HLA complex (HLA-A, -B, -C, -DR, -Bf, -C2 and -GLO) and 212 haplotypes were demonstrated. Eleven recombinations were observed (two A/B, two A/C, two B/Bf, one Bf/D and four D/GLO). The linkage disequilibrium was calculated not only between two alleles (delta) but between three, four...seven alleles (D). In order to compare the intensity of D values in the various haplotypes, the influence of the differences in gene frequencies was eliminated by the introduction of the standardized Ds (Ds = D/D max). The number of haplotypes in disequilibrium is relatively limited since most of the significant Ds involved about 17 haplotypes. For some haplotypes, the disequilibrium covered the whole distance from A to GLO but the stronger disequilibrium concerns the C to Bf or C to DR segment. Three hypotheses (isolation, admixture of population and selection) concerning the formation and maintenance of the disequilibria are discussed.
Epitopes↗
Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2.
Two electrophoretically distinct variants of glyoxalase I (Glo-I) are present in mouse (Mus musculus). The two forms are controlled by two codominant alleles Glo-1a (common) and Glo-1b (rare) at an autosomal locus. A linkage study showed that Glo-1 maps at approximately 3 centimorgans from the Ss locus of the H-2 histocompatibility region. A similar linkage relationship exists in man between GLO and HLA, the human homolog of the H-2 gene complex. Thus, the chromosomal segment evolutionarily preserved in the two species is longer than previously suspected, and it includes genes with no obvious functional relation to the other components of the major histocompatibility complex. Several features of the Glo-1 polymorphism in the mouse recommend it as a marker of choice for the H-2 region.
Animals↗
Structural heterogeneity of C2 Complement protein and its genetic variants in man: a new polymorphism of the HLA region.
A zymogram method, following thin-layer isoelectric focusing in a polyacrylamide gel, allows resolution of the lytic activity of serum C2 complement protein in a spectrum of molecular forms. This spectrum is characteristic in each of the species studied (man, rhesus monkey, guinea pig, and hamster). Moreover, two different alternative patterns are observed in man: each of the six major lytic bands characteristic of the most common pattern (herein designated C2(1) is duplicated in the least common pattern (C2(2-1), with an additional band displaced cathodally by not more than 0.04 pH unit. Distribution of phenotypes C2(1) and C2(2-1) in a Caucasion population is in agreement with the hypothesis that they are controlled by two alleles, C2(1) and C2(2), with frequencies 0.96 and 0.04 +/- 0.01. Segregation studies show that the two alleles are codominant and identify a locus in the HLA region. No recombinants with HLA-B were detected among 27 informative meioses, generating a cumulative lod score of 6.321 at equals 0. These findings suggest that the individuals with the C2-deficient trait might be interpreted as homozygotes for a third and rarest amorph C2 degrees of the same locus.
Animals↗
Independent segregation of two functional markers expressed on the same B-cell subset in the mouse: the Mls determinants and LPS receptors.
Mice of the C3H/Tif strain display a mixed leukocyte reaction (MLR) with all H-2k strains carrying any of the known alleles of the Mls locus. In particular, C3H/Tif is incompatible with the related substrain C3H/HeJ, from which it also differs at the locus responsible for the recognition of lipopolysaccharides (LPS) as B-cell mitogens, and at the Mod-1 locus. Our genetic analysis indicates that the MLR incompatibility between these strains is not H-2-linked and segregates as controlled by a single locus, most probably identical to Mls, for which the C3H/Tif strain expresses a previously unidentified allele, Mlse. Moreover, segregation data show that this locus assorts independently of LPS responsiveness and that neither marker is closely linked to the Mod-1 locus in linkage group II.
Alleles↗
Induction of an antibody response in cultures of human peripheral blood lymphocytes.
A culture system is descirbed which provides adequate conditions for in vitro immunization of humand peripheral blood lymphocytes to heterologous erythrocytes. Making use of this method we could obtain, with a number of different donors, an antibody response which peaked at about day 8 of culture with 30-300 plaque-forming cells (PFC) per 10(6) input lymphocytes. However, in a number of experiments poor or negative results were obtained, even with donors that had previously given good response. This variability in the results was shown not to be due to a too low number of precursor cells present in the blood and could be overcome by treating the cells, before initiation of the culture, with a factor produced by mouse T cells educated to sheep erythrocytes (SRBC). Under these conditions a PFC responce was obtained which peaked at about day 8 and which in some experiments could be as high as 20,000 PFC per 10(6) input lymphocytes. Paralleling the increase in PFC was an increase in cell number. The cells recovered from the treated cultures were at all times more numerous than in the nontreated cultures. The height of both the proliferative and antibody-producing responses varied from experiment to experiment, a higher proliferative response, accompanying a higher PFC response. Although the mechanisms that are at the basis of the antibody response in vitro described in this paper still need to be clarified, this system may become a useful tool in studying the immune response in man.
Animals↗
Expression of individual Ia specificities on T and B cells. I. Studies with mitogen-induced blast cells.
Ia specificities 1-10 were detected on LPS-stimulated splenic lymphocytes and on Con A-stimulated spleen, lymph node, and thymus blasts by direct cytotoxic tests. Since Ia antigens are not readily detectable on resting thymocytes, our results suggest that T cells require some signal before they exhibit full expression of Ia specificities. Absorption-elution studies indicated that most of the Ia specificities detected on T and B cells may be identical. Ia antigens detected by homologous antisera gave much stronger reactions than those detected by cross-reacting antisera.
Animals↗
Immunochemical characterization of murine H-2 controlled Ss (serum substance) protein through identification of its human homologue as the fourth component of complement.
The S region of the mouse H-2 complex is genetically defined by a series of alleles, or pseudoalleles, which control the level of a serum globulin, Ss, and of its allotypic vairatn, Slp. In contrast with the products of other genes in the complex, no homologue of the Ss protein has been found in other species, except the rat. In the present study, a component in human plasma was identified which cross-reacts with anti-mouse Ss, and which also displays electrophoretic and size similarities to the mouse Ss protein. This component was isolated and characterized immunochemically as the fourth component of human complement (C'4 or beta1E globulin). Several antisera monospecific for human C'4 cross-react with the mouse Ss protein and detect its genetically determined quantitative variations.
Animals↗
Further miniaturization and automation of in vitro lymphocyte cultures.
A microtechnique (10 mul culture volume) for in vitro lymphocyte cultures is described, which, compared with current miniaturized techniques, permits a four to 20-fold reduction of both medium volume and cell numbers. Furthermore, two alternative procedures for harvesting and washing radioisotope labelled cells are described. The first, making use of a conventional harvesting device, collects cells on glass fibre filters in a two to three-fold shorter time than that needed for the current semi-automatic collectors. The second takes advantage of the possibility of washing and fixing the cells in their culture wells and allows processing of more cultures with fewer manual operations. Various technical aspects of the micro-culture system are described and discussed with special reference to automation problems.
Animals↗
Location of the gene for theta antigen in the mouse. II. Three-point crosses place Thy-1 in proximal region of chromosome 9.
Males of a partially inbred mouse stock homozygous for cw and d were crossed to AKR/ABom females. Progeny obtained by backcrossing heterozygous F1 females to cw d/cw d males were analyzed for the markers cw, Thy-1, d, and Mod-1. Three- and four-point recombination data are consistent with the map: cw--29--Thy-1--12--d--5--Mod-1, in which cw is nearest to the centromere. These recombination data are discussed in relation to previous multiple-point recombination studies of chromosome 9.
Animals↗