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Biomedical subjects

E Stockert

Publications and source records attributed to E Stockert.

At least 109 records · Page 6Linked to original sources
PubMed1973

Relation of chromosome 4 (linkage group 8) to murine leukemia virus-associated antigens of AKR mice.

Genes specifying or controlling the expression of G(IX) (cell surface), GCSA (cell surface), and gs (internal viral) antigens are located in chromosome 4 (linkage group [LG] VIII) of the AKR mouse. All three antigens may exhibit mendelian inheritance, mice being antigen positive or antigen negative, but each may also appear in leukemic cells of mice whose inherited genotype was antigen negative. The G(IX)-determining gene in LG VIII of AKR mice apparently is equivalent to Gv-1, which determines expression of the same antigen in 129 strain mice, but which in the latter strain is located in LG IX. As the estimated distance of Gv-1 from H-2 in 129 mice is considerable (37 units) further tests are now indicated to assess the possibility of pseudolinkage in this case. The Fv-1 locus, also located in LG VIII, influences the mouse's titer of MuLV, and might thereby be thought to regulate the G(IX) and gs phenotypes of AKR backcross segregants. But the data indicate a discrete LG VIII locus for G(IX), since expression of this antigen is mendelian and independent of infectious virus titer. Since the G(IX) and GCSA phenotypes of AKR backcross segregants were invariably concordant, these two antigens must be specified or controlled by closely linked genes, and the latter also is presumably independent of virus titer. The question as to what extent expression of gs antigen in the segregants is secondary to virus production is undecided.

Animals↗
PubMed1971

The G-IX system. A cell surface allo-antigen associated with murine leukemia virus; implications regarding chromosomal integration of the viral genome.

This report concerns a cell surface antigen (G(IX); G = Gross) which exhibits mendelian inheritance but which also appears de novo in cells that become productively infected with MuLV (Gross), the wild-type leukemia virus of the mouse. In normal mice, G(IX) is a cell surface allo-antigen confined to lymphoid cells and found in highest amount on thymocytes. Four categories of inbred mouse strains can be distinguished according to how much G(IX) antigen is expressed on their thymocytes. G(IX) (-) strains have none; in the three G(IX) (+) categories, G(IX) (3), G(IX) (2), and G(IX) (1), the amounts of G(IX) antigen present (per thymocyte) are approximately in the ratios 3:2:1. A study of segregating populations derived mainly from strain 129 (the prototype G(IX) (3) strain) and C57BL/6 (the prototype G(IX) (-) strain) revealed that two unlinked chromosomal genes are required for expression of G(IX) on normal lymphoid cells. The phenotype G(IX) (+) is expressed only when both genes are present, as in 129 mice. C57BL/6 carries neither of them. At one locus, expression of G(IX) is fully dominant over nonexpression (G(IX) fully expressed in heterozygotes). At the second locus, which is linked with H-2 (at a distance of 36.4 +/- 2.7 units) in group IX (locus symbol G(IX)), expression is semidominant (50% expression of G(IX) in heterozygotes); gene order T:H-2:Tla:G(IX). As a rule, when cells of G(IX) (-) mice or rats become overtly infected with MuLV (Gross), an event which occurs spontaneously in older mice of certain strains and which also commonly accompanies malignant transformation, their phenotype is converted to G(IX) (+). This invites comparison with the emergence of TL(+) leukemia cells in TL(-) mouse strains which has been observed in previous studies and which implies that TL(-) --> TL(+) conversion has accompanied leukemic transformation of such cells. So far the only example of G(IX) (-) --> G(IX) (+) conversion taking place without overt MuLV infection is represented by the occurrence of GCSA(-):G(IX) (+) myelomas in BALB/c (GCSA:G(IX) (-)) mice. Unlike the other Gross cell surface antigen described earlier, GCSA, which is invariably associated with MuLV (Gross) infection and never occurs in its absence, G(IX) antigen sometimes occurs independently of productive MuLV infection; for example, thymocytes and some leukemias of 129 mice are GCSA(-):G(IX) (+), and MuLV-producing sarcomas may be GCSA(+):G(IX) (-). The frequent emergence of cells of G(IX) (+) phenotype in all mouse strains implies that the structural gene coding for G(IX) antigen is common to all mice. There is precedent for this in the TL system, in which two of the Tla genes in linkage group IX appear to be ubiquitous among mice, but are normally expressed only in strains of mice carrying a second (expression) gene. It is not yet certain whether either of the two segregating genes belongs to the MuLV genome rather than to the cellular genome. This leaves the question whether MuLV may have a chromosomal integration site still debatable. But there is a good prospect that further genetic analysis will provide the answer and so elucidate the special relationship of leukemia viruses to the cells of their natural hosts.

AKR murine leukemia virus↗
PubMed1970

Implications of TL phenotype changes in an H-2-loss variant of a transplanted H-2b-H-2a leukemia.

An H-2-loss variant line, lacking H-2(a) antigens, was obtained from an H-2(b)/H-2(a) (C57BL x A)F(1) transplanted leukemia by immunoselection. The TL phenotype of the unselected line was TL.1,2,3,4 and that of the variant TL.1,2,4, which is the phenotype of TL(+) leukemias of C57BL. This finding, and the observed quantitative alterations of antigens TL.1,2 and 4, indicate that the Tla (Thymus leukemia antigen) locus was functionally deleted together with the H-2 locus in the process of variant formation, despite absence of selection against cells carrying TL antigens. Representation of H-2 antigens of the remaining haplotype, H-2(b), was quantitatively unchanged.

Animals↗
PubMed1968

Isoantigens of the H-2 and Tla loci of the mouse: interactions affecting their representation on thymocytes.

H-2 and TL isoantigens of the mouse are specified by the closely linked genetic loci H-2 and Tla. A. study of their representation on thymocytes was performed in order to reveal any interactions between the determinant genes or their products affecting the synthesis or disposition of these components of the thymocyte surface. The method employed was quantitative absorption of cytotoxic antibody by viable thymocytes. The phenotypic expression of TL antigens was found to reduce the demonstrable amount of certain H-2 antigens to as little as 34% of the quantity demonstrable on TL- thymocytes. A reduction was observed in all three H-2 types tested, (H-2(b), H-2(a), and H-2(k)). As antigenic modulation (change of TL phenotype from TL+ to TL-, produced by TL antibody) is known to entail a compensatory increase in H-2(D) antigen, it is concluded that the TL phenotype, rather than the Tla genotype, influences the surface representation of H-2 antigens. The two known TL+ phenotypes of thymocytes (TL.2 and TL.1,2,3) depress H-2 equally. The H-2 specificities affected are those determined by the D end of the E-2 locus, which is adjacent to Tla; antigens of the K end, which is distal to Tla, are not depressed. The reduction of demonstrable H-2 antigen on the thymocytes of TL+ x TL- progeny is half that of thymocytes of TL+ x TL+ progeny and the reduction affects equally the products of both H-2 alleles (cis and trans in relation to Tla), indicating that the mechanism of H-2 reduction by TL is extrachromosomal. Whether it involves diminished synthesis of H-2 or steric masking by TL at the cell membrane is unknown, but in either case the reciprocal relation of TL and H-2(D) antigens implies that they probably occupy adjacent positions on thymocytes and that the gene order, H-2(K): H-2(D):Tla is reflected in cell surface structure. Extrachromosomal interaction, apparently involving control of synthesis, occurs also within the TL system of antigens. Thymocytes of TL.2 x TL.1,2,3 progeny express the full homozygous quantity of antigens TL.1 and TL.3 (but not of TL.2), in contrast to the half-quantity present in thymocytes of TL- x TL.1,2,3 progeny. Another example of interaction is implicit in the finding that thymocytes of TL-1,2,3 x TL.1,2,3 progeny have more TL.2 antigen than thymocytes of TL.2 x TL.2 progeny, but in this instance there is nothing to indicate whether the mechanism is chromosomal or extrachromosomal. Thus the quantitative surface representation of at least some H-2 and TL antigens is influenced by the cellular complement of H-2:Tla genes as a whole. Comparison of H-2 heterozygous thymocytes with H-2 homozygous thymocytes in quantitative absorption tests shows (a) more than the expected 50% of each parental-type H-2 antigen on heterozygous cells, and (b) a greater suppression of H-2 by TL in H-2 heterozygotes in comparison with H-2 homozygotes. Both results may be explained on the basis of differences in the density of H-2 antigenic sites and consequent differences in the efficiency of absorption of H-2 antibody. These considerations may be useful in other contexts, e.g. in estimating the representation of Rh antigens on the red cells of human subjects homozygous and heterozygous for Rh components.

Animals↗
PubMed1968

Asparagine synthetase activity of mouse leukemias.

Various transplanted leukemias and normal tissues of the mouse were tested for asparagine synthetase activity. Leukemias susceptible to suppression by asparaginase have little or no synthetase activity. In contrast, leukemias insensitive to asparaginase exhibit substantial and often very high asparagine synthetase activity. Asparaginase-resistant variants of sensitive leukemias also have considerable synthetase activity. Thus the requirement by certain malignant cells of exogenous asparagine, which entails sensitivity to asparaginase, may be ascribed to lack of asparagine synthetase. Development of asparaginase-resistant variants from asparaginase-sensitive lines is consistently associated with acquisition of asparagine synthetase activity.

Animals↗
PubMed1968

Antigenic modulation. Loss of TL antigen from cells exposed to TL antibody. Study of the phenomenon in vitro.

Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37 degrees C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0 degrees C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ --> TL- modulation and may require several cell divisions.

Amides↗
PubMed1967

Mouse isoantigens: separation of soluble TL (thymus-leukemia) antigen from soluble H-2 histocompatibility antigen by column chromatography.

Mouse H-2 histocompatibility antigen has been extracted, solubilized, and partly purified from the cells of an A strain spontaneous leukemia carrying TL (thymus-leukemia) antigens. H-2 and TL. 1, 2, 3 activities were measured by inhibition of the cytotoxic effect of the corresponding isoantibodies. TL activity was associated with the H-2 active fraction obtained by solubilization and fractionation by gel filtration. TL specificity was largely separated from H-2 antigen by subsequent chromatography on DEAE Sephadex as an adjacent component in a series of fractions. The soluble H-2 antigen prepared from the leukemia cells was tested for most of the specificities determined by H-2(a) with no exceptional results. TL. 1, 2, 3 activities, measured as each component separately, were located in approximately the same position; there is no clear indication yet whether the three TL specificities are separable from one another. It appears that in addition to the close genetic linkage between the H-2 and TL loci, and their reciprocal interaction in producing H-2 and TL antigens, these antigens exhibit some similarity at the chemical level.

Animals↗