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Biomedical subjects

D B Murphy

Publications and source records attributed to D B Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1979

Partial N-terminal amino acid sequence analyses and comparative tryptic peptide maps of murine Ia molecules encoded by the I-A subregion.

The partial N-terminal amino acid sequences and tryptic peptide maps of I-A subregion products from the H-2b, H-2d, H-2k and H-2s haplotypes demonstrate that haplotype-associated differences are present in both alpha and beta polypeptides. The genetic and evolutionary implications of these multiple amino acid substitutions and the homology relationships among Ia molecules from human, guinea pig and the I-E subregion of the mouse are discussed.

Alleles↗
PubMed1978

Two-gene control of the expression of a murine Ia antigen.

Two dimensional polyacrylamide gel electrophoresis of Non-Idet P-40 extracts and of specific Ia immunoprecipitates from [35S]methionine-labeled mouse spleen lymphocytes has revealed that the cell surface expression of some Ia antigens appears to be controlled by two genes. One locus, which maps in the I-A subregion, is probably the structural gene for an Ia polypeptide chain. The second locus, which maps between the I-J and H-2D regions, controls whether this I-A encoded molecule (Ae) remains in the cytoplasm or is modified and expressed on the cell surface. Complementation between these two loci allowing surface expression of Ae can occur in the cis or trans chromosomal position. Both the I-A molecule and a polypeptide chain coded for by a locus in I-E are coprecipitated by anti-I-E antibodies, suggesting that these two chains are associated with each other as a multisubunit complex in the cell. Because the ability to complement I-A for Ae expression is a property only of those strains which synthesize an I-E-encoded protein, it is likely that the I-E product itself is regulating the expression of Ae. These observations suggest several mechanisms by which interaction between two I region loci can generate new cell surface molecules. As a result, they may have important implications for understanding the molecular basis of two gene control of immune responsiveness and immune suppression.

Animals↗
PubMed1978

Cellular basis of tolerance to serum albumin in adult mice. I. characterization of T suppressor and T helper cells.

The surface markers and size of suppressor cells were determined in adult (BALB/c x C57BL/Ka)F1 mice which were tolerized with a single injection of deaggregated bovine serum albumin (BSA). Suppressor cells from the spleens of tolerazided donors were assayed in a cell transfer system in which graded numbers of cells were injected into irradiated syngeneic mice along with limiting numbers of T cells primed to BSA and an excess of B cells primed to DNP-BSA. Adoptive hosts were challenged with DNP-BSA in saline, and the anti-DNP response was measured. Suppressor cells were antigen specific as shown by the inhibitory activity of BSA-tolerant spleen cells on the response to DNP-BSA, but not to DNP-BGG. Suppressor cells were eliminated by in vitro treatment with anti-Thy 1.2, anti-Ly-2.2, anti-I-J subregion antisera and C, but not with anti-Ly-1 or anti-I-A subregion antisera. Neither unprimed nor primed helper T cells were detected in the spleen of tolerized donors after in vitro treatment with anti-Ly-2.2 antisera. Both helper and suppressor T cells from the spleens of primed or tolerized donors, respectively, showed a rapid sedimentation velocity (S greater than 3.7 mm/hr).

Animals↗
PubMed1977

Immunochemical evidence for three Ia loci in the I-region of the H-2 complex.

Sequential immunoprecipitation analyses of Ia antigens were performed with 125I-labeled B10, B10.A(3R), and B10.A(5R) spleen cell lysates. The results suggest the presence of one I-region associated (Ia) locus (Ia-1) in the I-A subregion. In addition, they indicate that two Ia loci map between the I-J and S regions. One locus, Ia-5, maps in the I-E subregion. The second locus, most likely Ia-3, maps in either the I-E or I-C subregion. Taken together, the data demonstrate that at least three Ia loci in the I-region of the H-2 complex code for molecules detectable by immunoprecipitation.

Animals↗
PubMed1977

The Fc receptor on thymus-derived lymphocytes. IV. Inhibition of binding of antigen-antibody complexes to Fc receptor-positive T cells by anti-Ia sera.

Treatment of splenic T lymphocytes with anti-Ia antiserum inhibits the binding of antigen-antibody (AgAb) complexes to the majority (less than 50%) of Fc receptor-positive (FcR+) T cells. A similar inhibition was observed with anti-H-2D and anti-H-2K sera but not with anti-Thy 1.2. Despite the presence of Ia determinants on peripheral T cells, as established by the inhibition of AgAb binding, Ia could not be detected on peripheral T cells by immunofluorescence assays. Data obtained with the AgAb-binding inhibition assay indicate that determinants controlled by loci mapping in the I-A and I-C, S, or G regions are present on the FcR+ T cells. Evidence is presented that subpopulations of T cells within the FcR+ T-cell population may be distinguishable on the basis of which I-region-controlled determinant is expressed. The data are discussed in terms of phenotypic and functional heterogeneity of T lymphocytes.

Animals↗
PubMed1977

Structure of murine Ia antigens: partial NH2-terminal amino acid sequences of products of the I-E or I-C subregion.

Partial amino acid sequence of the Ia molecule encoded by the I-E or I-C (I-EC) subregion of the major histocompatibility complex of the mouse are presented. The Ia molecule appears to be comprised of two noncovalently associated polypeptides. The larger subunit, alpha, has an approximate molecular weight of 35,000 and the smaller subunit, beta, an approximate molecular weight of 28,000. Several interesting homology relationships (or the lack thereof) are apparent when the Ia polypeptides from the I-EC subregion are compared both with their counterparts from man and guinea pig and with the molecules encoded in the I-A subregion. Clearly the most impressive homology relationship is that seen between the alpha polypeptide from the I-EC subregion of mouse and its human counterpart. This is in striking contrast to the beta polypeptide, which bears no apparent homology to its human counterpart.

Amino Acid Sequence↗
PubMed1977

Selective expression of separate I-region loci in functionally different lymphocyte subpopulations.

Determinants controlled by separate loci mapping in the I region of the H-2 gene complex are selectively expressed on subpopulations of lymphocytes which play different roles in generating humoral responses. The Ia-4 locus, which marks a new I subregion, designated I-J, controls determinants found on allotype suppressor and normal (nonsuppressed) T lymphocytes. These determinants are not present on helper T lymphocytes or B lymphocytes. In contrast, the Ia-1 locus, which marks the I-A subregion, controls determinants present on B lymphocytes but not on suppressor or helper T lymphocytes. Another locus (subregion not known) controls determinants which distinguish helper T lymphocytes from suppressor T lymphocytes. Such selective expression suggests that the products of these loci may plan an integral role in lymphocyte interactions.

Animals↗
PubMed1976

Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes.

Data presented here show that locidentify in the I-region of the H-2 gene complex are selectively expressed in different functional T-cell subpopulations. These loci are closely linked (or possibly identical) to loci that control immune responses. They control surface determinants which identify helper and suppressor T lymphocytes. Determinants described here on allotype suppressor T cells (Ts) are found on normal (nonsuppressed) lymphoid cells, but are not found on helper T cells (Th). These determinants are controlled by a locus mapping in the I region of the H-2 complex. In an accompanying publication we show that this locus (Ia-4) marks a new I subregion (I-J) and is expressed only on T cells. Thus Ia-4 determinants idenfity a T-cell subpopulation which includes Ts but not Th. Th also carry identifying surface determinants controlled by loci that map to the H-2 complex, probably within the I region. These determinants are not found on Ts. Data presented also establish that loci in the I region control determinants on Th, but do not conclusively demonstrate that these are the determinants that distinguish Th from Ts. The selective expression of H-2-controlled determinants on Ts and Th suggests that these determinants are directly involved in immunoregulation.

Animals↗
PubMed1976

A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.

In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.

B-Lymphocytes↗
PubMed1975

The mechanism of microtubule-dependent movement of pigment granules in teleost chromatophores.

The relationship of cytoplasmic microtubules to intracellular transport has been investigated in teleost chromatophores. Antimitotic agents, including colchicine, vinblastine, hydrostatic pressure, and low temperature remove microtubules in these cells and simultaneously disrupt the alignment and arrest the movement of pigment granules. During recovery, the return of alignment and movement corresponds in both time and space with the repolymerization of microtubules. These results demonstrate that microtubules are essential for the intracellular transport of pigment. Investigations of the mechanism of movement show that microtubules do not change in number or location during the redistribution of pigment in Fundulus melanophores. Microtubules in melanophores also behave as semi-stable organelles as determined by investigation with colchicine and hydrostatic pressure. These observations and others rule out a push-pull mechanism based on the polymerization and depolymerization of microtubules or one that distinguishes two operationally different sets of microtubules. It is proposed instead that particles move by sliding along a fixed array of microtubules.

Animals↗
PubMed1975

Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity.

Serological cross-reactivity between the products of the H-2K and H-2D genes has been demonstrated by a design in which antibody was produced against determinants controlled by one locus (e .g . H-2K(k)), and then tested against the product of the opposite locus (e .g . H-2D(d)). A total of 13 out of 18 such test combinations exhibited H-2K-H-2D cross-reactivity. The presence or absence of cross-reactivity was reciprocal in most cases (i.e. antibody directed against the H-2K(k) gene product reacted with H-2(d) determinants, and antibody directed against the H-2D(d) gene product reacted with H-2K(k) determinants). An Ia-like reaction was detected with one antiserum which implied possible cross-reactivity between the products of two discrete la genes.

Animals↗
PubMed1975

Association of high-molecular-weight proteins with microtubules and their role in microtubule assembly in vitro.

High-molecular-weight components (HMW) specifically associated with microtubule protein purified from porcine brain tissue were separated from tubulin by DEAE-Sephadex ion exchange chromatography. Analysis by viscometry, sedimentation, and electron microscopy of the unfractionated microtubule protein, separated HMW and tubulin fractions, and reconstituted mixtures showed that HMW promoted formation of ring structures at 5 degrees and tubule polymerization at 37 degrees. The HMW reassociated with tubulin and was identified in thin sections as 18.9 x 5.6 nm projections attached to the microtubules with a longitudinal periodicity of 32.5 nm. These studies: (1) indicate that the HMW fraction stimulates microtubule assembly by facilitating the formation of ring structures which are apparently intermediates in polymerization, and (2) demonstrate that the HMW associates with microtubules as a structural component projecting from the surface of the microtubule wall.

Animals↗