Paradigm regained: similarities and differences between T cell receptor and immunoglobulin genes.
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Animals↗
Biomedical subjects
Y H Chien
Publications and source records attributed to Y H Chien.
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↗
Isolation and characterization of calmodulin genes from Xenopus laevis.
Two cDNAs derived from Xenopus laevis calmodulin mRNA have been cloned. Both cDNAs contain the complete protein-coding region and various lengths of untranslated segments. The two cDNAs encode an identical protein but differ from each other by 5% nucleotide substitutions. The 5' and 3' untranslated regions, to the extent available, are highly homologous between the two cDNAs. The predicted sequence of X. laevis calmodulin is identical to that of vertebrate calmodulins from mammals and chickens and shows one substitution compared with electric eel calmodulin. Genomic DNA sequences homologous to each of the two cDNA clones have been isolated and were shown to account for the major calmodulin-coding DNA sequences in X. laevis. These data suggest that X. laevis carries two active, nonallelic calmodulin genes. Although no complete analysis has been carried out, it appears that the X. laevis calmodulin genes are interrupted by at least four introns. The relative concentrations of calmodulin mRNA have been estimated in different embryonic stages and adult tissues and found to vary by up to a factor of 10. The highest levels of calmodulin mRNA were found in ovaries, testes, and brains. In these three tissues, the two calmodulin genes appear to be expressed at approximately equal levels.
Amino Acid Sequence↗
A method for the isolation of segments from the 5' ends of retrovirus RNA.
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Nucleic Acid Hybridization↗
Genomic organization of rat prolactin and growth hormone genes.
Five overlapping cloned DNAs containing the rat prolactin gene and its flanking sequences, as well as one cloned DNA containing the rat growth hormone gene and its flanking sequences, were isolated from a chromosomal DNA library. They were characterized by restriction enzyme mapping and electron microscopy. In each gene, the structural gene sequence coding for mature mRNA of a length of about 1 kilobase is split into at least five segments by a minimum of four intervening sequences. The two genes are similar in the length and organization of their coding regions, consistent with the suggestion that they are derived from a common ancestral gene. However, the two genes differ greatly in the lengths of their intervening sequences. That leads to a total gene length of 10 kilobase pairs for the prolactin and 2.1 kilobase pairs for the growth hormone gene. At least one intervening sequence appears to be in the 5' nontranslated regions of the prolactin and growth hormone mRNA coding sequences.
Animals↗
Heteroduplex analysis of the RNA of clone 3 Moloney murine sarcoma virus.
Heteroduplex analysis of the RNA isolated from purified virions of clone 3 Moloney murine sarcoma virus (M-MSV) hybridized to cDNA's from Moloney murine leukemia virus (M-MLV) and clone 124 M-MSV shows that the main physical component of clone 3 RNA is missing all or most of the 1.5-kilobase (kb) clone 124 M-MSV specific sequence denoted beta s (S. Hu et al. Cell 10:469--477, 1977). This sequence is either deleted in clone 3 RNA or substituted by a very short (0.3-kilobase) sequence. In other respects, clone 3 and clone 124 RNAs show the same heteroduplex structure relative to M-MLV. Since beta s is believed to contain the src gene(s) of clone 124 RNA, this result leaves as an unresolved question the nature of the src gene(s) of the clone 3 M-MSV RNA complex.
Base Sequence↗
RNA:DNA hybrids are more stable than DNA:DNA duplexes in concentrated perchlorate and trichloroacetate solutions.
Rates of formation of RNA:DNA hybrids have been measured as a function of temperature and compared to DNA:RNA duplex denaturation temperatures in 4 M sodium perchlorate, 4 M NaClO4-6 M urea, and 3 M rubidium trichloracetate solvents. The usual bell shaped curves of reaction rate versus temperature were observed. The optimal temperatures for the RNA:DNA association reaction are 5 degrees to 12 degrees greater than the Tm's for DNA:DNA denaturation in these solvents, just as in formamide. R-loops of phi80d3ilv DNA with E. coli rRNA can be formed at high efficiency in these solvents.
DNA, Bacterial↗
High-molecular-weight RNAs of AKR, NZB, and wild mouse viruses and avian reticuloendotheliosis virus all have similar dimer structures.
Several 50 to 70S tumor viral RNAs have previously been shown by electron microscopy to be dimers, with the two monomer subunits joined near their 5' ends. Five additional naturally occurring type C RNA tumor viruses have now been examined: AKR, and endogenous murine ecotropic virus; NZB, an endogenous murine xenotropic virus; and ecotropic and an amphotropic virus isolated from a wild mouse; and the avian reticuloendotheliosis virus (REV). All five 50 to 70S RNAs have similar 5'-to-5' dimer structures. Therefore, the observations support the hypothesis that the dimer linkage is a structural feature common to all type C mammalian viruses. REV is the first example of an avian virus with a clear 5'-to 5' dimer linkage. All of the mammalian viral RNAs, but not REV, showed symmetrically placed loops in each subunit of the dimer. Possible molecular structures and biological functions of the dimer linkages and loops are discussed.
AKR murine leukemia virus↗
Heteroduplex analysis of the sequence relations between the RNAs of mink cell focus-inducing and murine leukemia viruses.
The sequence relationships betwen AKR ecotropic virus and an AKR-derived "mink cell focus-inducing" (MCF) isolate (AKR MCF 247), between Moloney murine leukemia virus (M-MLV) and an M-MLV MCF isolate (M-MLV83), and between AKR and M-MLV were studied by electron microscopic heteroduplex analysis. The MCF-specific sequences were found to map from 1.95 kilobases (kb) to 2.75 kb (+/- 0.15 kb) from the 3' end of the RNAs for both MCF isolates. The major sequence nonhomology regions between AKR and M-MLV lie between 0.9 and 3.5 kb from the 3' end. However, the AKR and M-MLV sequences immediately adjacent to the 1.95- and 2.75-kb junctions with MCF-specific sequences are relatively similar in AKR and M-MLV. Our results suggest that the env gene of MLVs maps from 1 kb to 3 kb from the 3' end of the genomic RNA and that the carboxyl end of the glycoprotein of each MCF strain is similar (or identical) to that of its ecotropic parent.
AKR murine leukemia virus↗
Fluorescence quenching of adriamycin by specific antibodies.
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Amino Acids↗
Somatic recombination in a murine T-cell receptor gene.
A putative T-cell receptor gene was isolated from the DNA of the helper hybridoma, 2B4 . Analysis of the sequence components of this rearranged gene indicates the presence of separate variable (V), diversity (D) and joining (J) region elements analogous to those of heavy-chain immunoglobulins. These findings further support the belief that the products of this locus are involved in antigen recognition by T cells. There is no evidence of somatic mutation between the putative germ-line and the expressed variable-region gene.
Amino Acid Sequence↗
A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation.
A new T-cell receptor gene lies just 5' to the J alpha C alpha coding regions. Its placement in this location suggests a novel mechanism for the regulation of expression of one T-cell receptor polypeptide to another during ontogeny. Rearrangement of this locus occurs very early in thymic differentiation and its RNA expression parallels that of the gamma-chain in thymic subpopulations, making this a possible candidate for the recently described delta-chain of the T-cell receptor.
Animals↗
Identification and sequence of a fourth human T cell antigen receptor chain.
Thymus-derived lymphocytes (T cells) use clonally distributed antigen receptors to recognize peptide fragments associated with products of the major histocompatibility complex (MHC) (refs 1-4). On most murine and human T cells the T cell receptor (TCR) is composed of disulphide-linked alpha and beta chains (TCR alpha/beta), each of which contains constant and variable domains, and which are associated with the invariant chains of the CD3 complex. It has been demonstrated, however, that a distinct CD3-associated TCR is expressed on a small subset of T cells or immature thymocytes which fail to express either CD4 or CD8 (refs 7-14), the molecules associated with class II or class I MHC antigen recognition. Instead of TCR alpha/beta, these cells express heterodimers of gamma and delta chains (TRC gamma/delta). The genes encoding alpha, beta, and gamma have been isolated and characterized. A new murine T cell receptor (Cx) gene which undergoes rearrangement and expression early during T cell ontogeny has recently been identified 5' of the murine J alpha C alpha gene locus. Here we isolate and sequence the homologous transcript from PEER, a human cell line that expresses a TCR gamma/delta, and show that it encodes a protein with characteristic V, D, J, and C segments. Using probes derived from this transcript, we have shown that both PEER and MOLT-13, another TCR gamma/delta-expressing cell line, rearrange this locus and express two sizes of transcripts differing in the 3' untranslated region. Using a synthetic peptide derived from the deduced C region sequence, we have prepared antisera that precipitates the delta chain of the TCR from both PEER and MOLT-13, thus demonstrating that Cx and its human homologue code for the delta chain of the TCR.
Amino Acid Sequence↗
T-cell receptor delta gene rearrangements in early thymocytes.
The T-cell receptor delta-chain variable region can be assembled from as many as four distinct gene segments, V, D1, D2 and J, more than any other antigen-receptor gene. In fetal thymocytes V----D joinings are as common as D----J or VDJ rearrangements and one V gene segment predominates. Analysis of rearrangements at TCR gamma and delta loci during fetal ontogeny suggests abrupt changes and possible coordinate control in the rearrangement and expression of these loci.
Age Factors↗
Typhoid fever presenting as infection-associated hemophagocytic syndrome: report of one case.
This report describes a 13-year-old boy who had high fever with severe pancytopenia and acute psychosis as initial presentation. Bone marrow examination was compatible with infection-associated hemophagocytic syndrome (IAHS). Blood culture showed no growth of bacteria while the culture of bone marrow yielded Salmonella typhi. The clinical condition stabilized shortly after the use of ceftriaxone. This case illustrates that typhoid fever must be included in the differential diagnosis of IAHS. In cases with IAHS, bacterial culture as well as morphological study of bone marrow is necessary for the evaluation of etiological agent and to avoid injudicious use of chemotherapy.
Adolescent↗