Transfer of specificity by murine alpha and beta T-cell receptor genes.

T-cell receptor alpha- and beta-chain genes were isolated from a class I major histocompatibility complex-restricted cytotoxic T-cell clone and transferred by protoplast fusion into another cytolytic T-cell clone of different specificity. Expression of the transfected alpha and beta genes endowed the recipient cell with the specificity of the donor cell.

Interferon-gamma, mitomycin C, and cycloheximide as regulatory agents of MHC class II-associated invariant chain expression.

The murine and human major histocompatibility complex class II-associated invariant chain genes are expressed in mature B cells and in antigen-presenting cells. Several pre-B cell lines and fibroblasts do not naturally contain invariant chain mRNA. Expression is inducible, however, by interferons and other agents interfering with proliferation.

The context of T-cell receptor gamma chain genes among wild mouse species.

We have examined the context of mouse T-cell receptor gamma (Tcr gamma) chain variable (V gamma) and constant (C gamma) genes among a panel of geographically isolated species of mice. Our Southern hybridization survey with C gamma reveals that essentially three C gamma genes are found among mouse species extending phylogenetically from inbred mice through the feral species Mus pahari. However, a V gamma DNA probe detects three to nine V gamma restriction fragment bands among the same group of mice.

[Genetic analysis of sacR, a cis-regulator of levan-saccharase synthesis of Bacillus subtilis].

The phenotypical and physical characterization of point mutations and deletions affecting sacR were analysed. The 2 X 28-bp palindromic region present within sacR was responsible for sacB inducibility by sucrose. The sacR mutations also affected sacB expression in Escherichia coli, suggesting that the palindromic region is a transcriptional terminator.

Hormonal regulation of cell surface expression of the major histocompatibility antigen H-2Ld in transfected cells.

The murine major histocompatibility antigens are cell surface glycoproteins which play an important role in the recognition of foreign antigens by cytotoxic T lymphocytes. Modulation of the level of expression of histocompatibility antigens could therefore be useful for the study of the interaction between the antigen presenting cells and T lymphocytes. The glucocorticoid hormone-inducible promoter, located in the long terminal repeat of mouse mammary tumor virus, was used to replace the promoter region of a cloned H-2Ld class I gene.

Positive selection procedure for entrapment of insertion sequence elements in gram-negative bacteria.

We constructed the broad-host-range plasmid pUCD800 containing the sacB gene of Bacillus subtilis for use in the positive selection and isolation of insertion sequence (IS) elements in gram-negative bacteria. Cells containing pUCD800 do not grow on medium containing 5% sucrose unless the sacB gene is inactivated. By using pUCD800, we isolated a 1.

The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen.

Mice bearing the recessive gene lpr develop an age-dependent, massive lymphoproliferation, primarily in the lymph nodes (LN), with associated autoimmunity. LN cells from these mice express T cell receptor protein on the cell surface at 50-70% of normal levels. Normal levels of T cell receptor alpha, beta and gamma mRNA were found in these cells as compared to normal LN cells.

Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo.

The continuously proliferating clones L/B AgA2, CB/Bm 7, Ba/C1, and Bc/Bm 11 were established from bone marrow of MRL/LPR, CBA/J, and BALB/c mice. These clones carry the B cell lineage surface antigen B-220 but not antigens normally expressed on mature B lymphocytes, myeloid cells, or T lymphocytes. Their immunoglobulin mu heavy chain and kappa light chain genes are in germ-line configuration.

Liver mRNA probes disclose two cytochrome P-450 genes duplicated in tandem with the complement C4 loci of the mouse H-2S region.

A search for uncharacterized genes of the S region of the murine H-2 major histocompatibility complex was undertaken; a series of cosmid clones previously aligned by overlap hybridizations were used as radiolabeled probes. Sequences hybridizing with liver poly(A)+ RNA were found within a cosmid covering a region 3' to the C4-Slp gene (the gene encoding the hemolytically inactive isoform of the fourth component of serum complement). Radiolabeled, short cDNA complementary to liver poly(A)+ RNA was used to establish the transcriptional polarity of the newly detected gene and to define fragments containing its 3' end.

The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukaemia.

We have examined the chromosomal location of human T cell-specific genes which are involved in antigen recognition and of a gene which specifically rearranges in T cells. The genes encoding both the variable and constant region segments of the T cell receptor alpha chain are found on chromosome 14 while the delta chain gene of the T cell receptor-associated T3 complex is localised to chromosome 11. Further, the two tandemly arranged T cell-specific rearranging genes, designated gamma, were mapped to chromosome 7, but apparently not closely linked to the previously mapped T cell receptor beta-chain gene.

Expression of T-cell antigen receptor genes during fetal development in the thymus.

The T-cell antigen receptor is a heterodimeric molecule composed of alpha- and beta-subunits of relative molecular mass 40,000-50,000 (refs 1-6). Recently, the genes encoding both the beta- and alpha- chains have been cloned. By comparing amino-acid and nucleic-acid sequences, it is clear that these genes encode the alpha- and beta-proteins of the T-cell receptor.

One gene encodes two distinct Ia-associated invariant chains.

Murine immune response region-encoded Ia antigens are associated not only with invariant (Ii) chain but also with several other polypeptides, most notably a 41K protein. The present report demonstrates a striking similarity between Ii and 41K. These polypeptides were found to be serologically cross-reactive, and they also display a similar peptide composition on partial enzymatic digestion.

The gene encoding the T-cell receptor alpha-chain maps close to the Np-2 locus on mouse chromosome 14.

Serological and molecular genetic analyses of T-cell clones have shown that the T-cell antigen receptor apparently comprises two glycosylated, disulphide-linked polypeptide chains (alpha and beta), both of which span the cell membrane. Cloning of the genes encoding the two chains from mouse and human DNA has shown that the alpha- and beta-chains are composed of variable (V) and conserved (C) regions in agreement with peptide mapping data. Gene segments encoding variable and conserved domains of the beta-chain have been identified and undergo rearrangements during T-cell differentiation.

Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp.

Mouse liver cDNA clones related to the C4 and C4-Slp isoforms of the fourth component of complement differ by few nucleotide changes within a region of substantial divergence from human C4. It is suggested that the mouse C4 gene duplication is an evolutionarily recent event with respect to the time of mammalian radiation. This conclusion is reinforced by the presence of a single C4 gene in the Syrian hamster.

Isolation of mouse N-CAM-related cDNA: detection and cloning using monoclonal antibodies.

Clones coding for the mouse neural cell adhesion molecule (N-CAM) were isolated from a cDNA library prepared in the expression vector lambda gt 11 from mRNA extracted from a mouse neuroblastoma cell line. This library was screened with two anti-N-CAM monoclonal antibodies directed against different sites on the molecule and with rabbit anti-N-CAM serum. Two clones were identified with the first monoclonal antibody, three with the second one, none reacted with both.

Ontogeny of the T-cell antigen receptor within the thymus.

The expression of T-cell antigen receptors during T-cell ontogeny is an important issue that bears directly on such questions as where T-cell tolerance is acquired, at what stage T cells become susceptible to repertoire selection, and why most thymocytes die within the thymus. The thymus rudiment is colonized during days 11 and 12 of gestation, but it is not until day 19 that significant numbers of functional thymocytes are present. Although much is known about the ontogeny of function- and specificity-associated surface molecules such as Ly2 and MT4 (the murine equivalent of human T4) during this period, the ontogeny of the T-cell antigen receptors remains obscure.

Inbred and wild mice carry identical deletions in their E alpha MHC genes.

Several inbred strains and a certain percentage of wild mice bear a deletion in the E alpha gene of the mouse major histocompatibility complex (H-2). This mutation prevents transcription of the E alpha gene and hence functional expression of the E alpha E beta dimer on the cell surface. Two strains were selected for a more precise localization of this deletion.

The DNA sequence of the gene for the secreted Bacillus subtilis enzyme levansucrase and its genetic control sites.

We present the sequence of a 2 kb fragment of the Bacillus subtilis Marburg genome containing sacB, the structural gene of levansucrase, a secreted enzyme inducible by sucrose. The peptide sequence deduced for the secreted enzyme is very similar to that directly determined by Delfour (1981) for levansucrase of the non-Marburg strain BS5. The peptide sequence is preceded by a 29 amino acid signal peptide.

Tracts of high or low sequence divergence in the mouse major histocompatibility complex.

The K, I and S regions of the mouse major histocompatibility complex (MHC) are composed of long tracts of DNA which differ in sequence divergence. A correlation exists between the location of an MHC gene in a variable or conserved chromosomal tract and the degree of polymorphism and diversity of the proteins encoded by its alleles. Variable tracts appear to be the result of mechanisms which mutate certain coding and non-coding sequences to the same extent and selective pressures operating on the genes.

Genomic constitution of an H-2:Tla variant leukemia.

A TL+ leukemia of a (B6 X A)F1 hybrid mouse (H-2b/H-2a) was previously subjected to immunoselection against H-2a by passage in (B6 X A.SW)F1 mice (H-2b/H-2s). A variant leukemia line was obtained that serologically lacked not only the H-2a phenotype but also the TL phenotype determined by the linked cis Tlaa allele of strain A.

Myopotential interference with DDD pacemakers: endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias.

Skeletal myopotentials may inhibit the output of unipolar demand ventricular pacemakers, resulting in protracted episodes of asystole in susceptible patients. The new DDD-mode pacemakers have, in addition to a unipolar ventricular lead, a unipolar atrial lead to enable atrioventricular sequential or atrial synchronous function. During clinical investigation of a new dual-unipolar cardiac pacing system programmed to operate in the DDD mode (Pacesetter AFP models 281 and 283), 6 patients were noted (5 men and 1 woman, aged 22 to 68 years) who manifested paroxysmal acceleration of ventricular pacing rate approaching the maximal tracking rate.