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M M Davis

Publications and source records attributed to M M Davis.

At least 181 records · Page 10Linked to original sources
PubMed1985

Molecular genetics of the T cell-receptor beta chain.

Characterization of cDNA and genomic clones encoding the Beta chain of the T-cell receptor for antigen reveals a very close resemblance to immunoglobulin: V, D, J, and C elements; the mechanism of rearrangement; and the potential extent of diversity, explaining the relatively large T-cell repertoire of specificities and the clonal nature of individual responses. Differences with immunoglobulins are evident in the much more heterogeneous V beta sequences, which appear to have additional hypervariable regions. Together these data predict a roughly immunoglobulin-like structure for the receptor, but with potentially significant variation from immunoglobulin in the nature of the combining site(s).

Animals↗
PubMed1985

Neoplasia and chromosomal breakage in ataxia-telangiectasia: a 2:14 translocation.

Four common sites of chromosome breakage have been observed in patients with ataxia-telangiectasia (AT): 7p14, 7q35, 14q11.2, and 14q32. These sites appear to coincide with the location of genes for the T-cell receptor subunits (alpha, beta, and gamma) and IGH. Each of these genes involves rearrangements of DNA for its expression, suggesting that an abnormal DNA processing enzyme or family of enzymes underlies this propensity for chromosomal breakage in AT patients. Such a defect could also explain the radiation hypersensitivity of AT fibroblasts. In view of these findings, it is perhaps surprising that AT patients do not manifest more severe immunological defects although they would explain the lack of uniformity of these defects from one patient to the next. Two other genes utilize DNA rearrangement, IGK (on chromosome 2p12) and IGL (on chromosome 22q11), and have not been noted previously to be involved in translocations in these patients. We report here a 2:14 translocation (p14:q32) in a phytohemagglutinin-stimulated lymphocyte from a patient with AT.

Adult↗
PubMed1984

Murine T cell receptor beta chain is encoded on chromosome 6.

Southern blot analysis of somatic cell hybrid lines indicates that the beta chain of the T cell receptor for antigen maps to chromosome 6 of the mouse. An experiment testing hybridization of the constant region of this gene to DNA from a hybrid cell line containing a translocation of chromosome 6 supports the localization of this gene to the proximal (centromeric) one-third of chromosome 6, in the same general region as the immunoglobulin kappa chain locus. This may be another indication of the shared evolutionary origins of the genes encoding both T and B cell antigen recognition.

Animals↗
PubMed1984

Cell-type-specific cDNA probes and the murine I region: the localization and orientation of Ad alpha.

Labeled cDNA probes highly enriched for B-cell-specific (B-T) and T-suppressor-cell-specific (Ts-B) sequences were used to screen a set of genomic cosmid clones spanning 230 kilobases of the murine immune response (I) region. With the B-cell derived probe, four I-region genes were detectable (A beta, E beta, E beta 2, and E alpha), as well as an additional (fifth) region of hybridization. The T-cell probe, prepared from a putative I-J positive suppressor cell hybridoma, was negative in a parallel experiment. A genomic fragment corresponding to the new region of hybridization seen with the B-cell cDNA probe identified a discrete mRNA species in RNA blotting analysis that had a pattern of expression strikingly similar to E alpha mRNA in a variety of lymphoid tumor lines. This fragment was also used to isolate cDNA clones from a library highly enriched (20-40 times) for B-cell-specific sequences (selected cDNA cloning). DNA sequence analysis of one of these cDNA clones indicates that this gene encodes the A alpha molecule of the d haplotype (Ad alpha). These findings establish that the order of the class II genes in the Ia complex is as follows: centromere-A beta-A alpha-E beta-E beta 2-E alpha.

Animals↗
PubMed1984

A murine T cell receptor gene complex: isolation, structure and rearrangement.

We describe here our efforts to develop a systematic strategy for the enumeration and isolation of genes encoding T cell-specific, membrane-associated polypeptides. Of particular importance among the cDNA clones that we have isolated is one which encodes the beta chain of the murine T cell receptor for antigen. The gene product is strikingly similar to immunoglobulin in its variable (V), constant (C), joining (J), and diversity (D) - like elements and the ability of the latter three types of element to assort independently during differentiation. The genomic organization of the constant region locus which encodes this molecule consists of two tandemly arrayed units of the form JC/JC, where the J clusters consist of fourteen distinct elements, many of which may be functional. The two constant regions differ by only four amino acids and both are apparently expressed in T cells of the same phenotype, so they probably do not represent isotypes in the classical sense. The sequences flanking the V, D and J elements are also similar to the conserved heptamer and nonomer sequences of immunoglobulins thought to be important in the recombination of the specific gene segments. These similarities indicate both the common evolutionary origins of these loci and the strong selective pressure that must be operative. The T cell receptor locus differs somewhat from immunoglobulins in the large number of possible J region elements and to some extent in the hypervariable-framework regions of the V region. We and others have mapped this gene to chromosome 6 of the mouse, in the same portion of the chromosome but not closely linked the kappa locus. The significance of the predicted protein structure of the beta chain and its support of the one-receptor model of MHC-antigen recognition are discussed.

Amino Acid Sequence↗
PubMed1980

Helper and killer T cells do not express B cell immunoglobulin joining and constant region gene segments.

We have analyzed four kinds of T cells for rearrangement and expression of immunoglobulin genes. These cells include: (a) whole thymus; (b) WEHI-22, a T-cell lymphoma; (c) HT-1, an major histocompatibility complex-restricted T helper line; and (d) CTLLi6, an H-2 alloreactive killer cell line. None of the B-cell joining and constant gene segments are rearranged in the T cells. The monoclonal cells do not express any C kappa, C lambda, Cmu or C alpha RNA species. Small amounts of C kappa, C alpha, and Cmu sequences are present in RNA prepared from the thymus, although the significance of this RNA for T-cell antigen receptor synthesis is uncertain. The data support the hypothesis that expression of B-cell joining and C gene segments is unnecessary for T-cell helper and T-cell killer activity.

Animals↗
PubMed1980

DNA sequences mediating class switching in alpha-immunoglobulins.

Immunoglobulin class switching involves specific DNA rearrangements of the gene segments coding for heavy chain constant regions (CH) during B lymphocyte differentiation. In two different cases of C mu to C alpha switching examined here (T15 and M603) and one taken from the literature (MC101), three different sites on the 5' side of C mu and three different sites on the 5' side of C alpha are joined together in the process of CH switching. The sequences surrounding the three germ-line C alpha sites of recombination are highly conserved blocks of 30 nucleotides that may serve as recognition sequences for CH switching to the C alpha gene. This putative recognition sequence is repeated 17 times in approximately 1400 nucleotides of the germ-line Calpha 5' flanking sequence. The lack of homology between this C alpha sequence and sequences reported for the C gamma 1 and C gamma 2b switch sites suggests that heavy chain switching is mediated by class-specific recognition sequences and, presumably, class-specific regulatory mechanisms. In addition, it appears that in one example (MC101) CH switching progressed from C mu to C alpha to C gamma 1. This switching pathway may present difficulties for the simple deletional model of CH switching.

Animals↗
PubMed1980

Fetal exposure to narcotics: neonatal sleep as a measure of nervous system disturbance.

Newborn infants, chronically exposed in utero to low doses of methadone with or without concomitant heroin, display more rapid eye movement sleep and less quiet sleep than control infants, while babies fetally exposed to both opiates and nonopiates have less organization of sleep states. Other perinatal factors, such as birth weight and gestational age, are related more to the amount of fetal drug exposure than to the type.

Birth Weight↗
PubMed1980

An immunoglobulin heavy-chain gene is formed by at least two recombinational events.

The events of B-cell differentiation can be reconstructed in part through an analysis of the organisation of heavy-chain gene segments in differentiated B cells. A mouse immunoglobulin alpha heavy-chain gene is composed of at least three noncontiguous germ-line DNA segments--a VH gene segment, a JH gene segment associated with the Cmu gene segment, and the C alpha gene segment. These gene segments are joined together by two distinct types of DNA rearrangements--a V-J joining and a CH switch.

Animals↗
PubMed1979

Immunoglobulin heavy chain gene organization in mice: analysis of a myeloma genomic clone containing variable and alpha constant regions.

We have isolated a myeloma genomic DNA clone containing the variable and constant regions of a mouse alpha chain. Restriction enzyme analyses and electron microscopic R loop mapping have demonstrated that the variable region is separated from the constant region by 6.8 kilobases of intervening DNA. In addition, two intervening DNA sequences of 100--200 bases separate the constant region into three approximately equal units. These intervening sequences may separate each of the segments coding for the three constant region domains of the alpha heavy chain. Southern blot analysis of embryo and myeloma DNA suggests that DNA rearrangement of heavy chain variable and constant regions occurs during the differentiation of antibody-producing cells.

Animals↗
PubMed1976

Structural gene sets active in embryos and adult tissues of the sea urchin.

Structural gene sequences active in a variety of sea urchin adult and embryo tissues are compared. A single-copy 3H-DNA fraction, termed mDNA, was isolated, which contains sequences complementary to the messenger RNA present on gastrula stage polysomes. Gastrula message sequences are 50 fold concentrated in the mDNA compared to total single-copy DNA. mDNA reactions were carried out with excess mRNA from blastula, pluteus, exogastrula, adult ovary, tubefoot, intestine, and coelomocytes, and with excess total mature oocyte RNA. A single-copy 3H-DNA fraction totally devoid of gastrula message sequences, termed null mDNA, was also reacted with these RNAs. Large differences in the extent of both mDNA and null mDNA reaction with the various RNAs were observed, indicating that in each state of differention a distinct set of structural genes is active, generally characterized by several thousand specific sequences. The complexity of gastrula mRNA was shown in previous work to be about 17 X 10(6) nucleotides. In units of 10(6) nucleotides, the complexities of the RNA sequence reacting with mDNA and with null mDNA in each tissue are, respectively, as follows: intestine mRNA: 2.1 and 3.7; coelomocyte mRNA: 3.5 and less than or equal to 1.4; tubefoot mRNA: 2.7 and less than or equal to 0.4; ovary mRNA: 13 and 6.7; oocyte total RNA: 17 and 20; blastula mRNA: 12 and 15; pluteus mRNA: 14 and less than or equal to 0.6; exogastrula mRNA: 14 and less than or equal to 0.6. The total complexity of each mRNA polulation is the sum of these values, as verified for several cases by reactions with total single-copy DNA. A relatively small set of mRNAs, the complexity of which is about 2.1 X 10(6) nucleotides, appears to be shared by several of the tissues studied.

Animals↗