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J Klein

Publications and source records attributed to J Klein.

At least 739 records · Page 41Linked to original sources
PubMed1983

In vitro correlate for a clonal deletion mechanism of immune response gene-controlled nonresponsiveness.

We used T cell-antigen-presenting cell (APC) combinations from two pairs of recombinant mouse strains, B10.A(4R)-B10.A(2R) and B10.S(7R)-B10.S(9R) (abbreviated 4R, 2R, 7R, 9R, respectively), which differ from each other only in the nonexpression vs. expression of cell-surface E molecules, to study the mechanism of the Ir gene-controlled (E-restricted) response to the terpolymer poly(glu51lys34tyr15) (GLT). No response to GLT occurred when the APC were from E-nonexpressor strains 4R and 7R. When APC from E-expressor strains were used and alloreactivity against the incompatible E molecules was removed by BUdR + light treatment, 7R T cells responded to GLT presented by 9R APC, but 4R T cells failed to respond to GLT presented by 2R APC. However, 4R T cells mounted a proliferative response to GLT presented by fully allogeneic 5R or 9R APC. The latter response was completely abolished by the depletion of cells alloreactive against 2R and 5R or 2R and 9R. Since removal of alloreactivity against 5R plus 9R did not affect the response of 4R T cells to GLT presented by either 5R or 9R cells, we conclude that the 4R T cells generated in response to GLT cross-react with the additional incompatibility presented by 2R cells, that is, the Ek beta chain. In contrast, 7R T cells recognizing GLT presented by 9R APC do not cross-react with Ek beta. These results demonstrate that "blind spots" in the T cell repertoire produced by depletion of cells alloreactive against a single chain of a class II MHC molecule can render a strain nonresponsive to a synthetic polypeptide antigen, and that this nonresponsiveness corresponds to that attributed to the MHC-linked Ir genes.

Animals↗
PubMed1983

Tissue structure and macromolecular diffusion in umbilical cord. Immobilization of endogenous hyaluronic acid.

Diffusion of endogenous hyaluronic acid and 125I-labelled albumin, monitored by desorption from umbilical cord (Wharton's jelly) slices, was studied in relation to tissue structure. Diffusion of hyaluronic acid was Fickian and some two orders of magnitude slower than that in free solution. After treatment of tissue with trypsin which removes proteoglycan(s) and degrades glycoprotein microfibrils, hyaluronic acid mobility through the collagen fibril network that remains is increased by an order of magnitude. These findings indicate that the mobility of hyaluronic acid in tissue is reduced both by the collagen network and by the presence of proteoglycan(s) and/or microfibrils. Estimates of the reduction in mobility due to physical entanglements with the fibrillar networks show that these play a major role. The mobility of hyaluronic acid found for intact tissue is sufficient for it to permeate the extracellular space within its metabolic turnover time. Labelled albumin diffusion is intact tissue, on the other hand, is reduced by only some 30% relative to free solution. This is consistent with the approximate 10% reduction found for the polysaccharide-free tissue (given by the excluded volume fraction) and the approximate 20% reduction expected for the polysaccharides in the interstitial fluid. Similar effects appear to be involved in the mobility of endogenous diffusible proteins in tissue.

Connective Tissue↗
PubMed1983

Different repertoires of mouse T cells for bovine insulin presented by syngeneic and allogeneic cells.

Splenic T cells were primed, after removal of alloreactive cells, to beef insulin on allogeneic antigen-presenting cells (APC). The fine specificity of in vitro secondary response was tested in combinations H-2b (responder) T cell-H-2k (nonresponder) APC, and vice versa, using separated chains of beef and pork insulin. The response in both combinations exhibited identical specificity patterns demonstrating that both responder and nonresponder APC could present the same array of insulin epitopes to allogeneic T cells. The determinants presented to allogeneic T cells include the A-chain loop epitope and the B-chain determinant(s) that were found to be immunogenic for H-2b and H-2d T cells, respectively, in the context of syngeneic major histocompatibility complex (HC) molecules. In addition, minor determinants were detected in the A chain outside the loop that are not immunogenic in syngeneic T cell-APC combinations. Inhibition of T cell proliferation with monoclonal antibodies has shown that class II MHC molecules of the nonresponder (Ak alpha Ak beta, Ek alpha Ek beta) as well as those of the responder APC (Ab alpha Ab beta) are equally capable of presenting virtually all insulin epitopes recognizable by T cells. The data, therefore, demonstrate that the selective recognition of different insulin epitopes observed in syngeneic or semisyngeneic T cell-APC combinations does not result from determinant selection at the level of APC.

Amino Acid Sequence↗
PubMed1983

H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex.

In this second part of the Second Listing, we describe genes that constitute the H-2 complex proper. Here, we define the complex functionally as consisting of class I and class II loci (see Klein et al. 1983a). The H-2-associated complement loci and the Neu-1 locus have been described in the first part of the Second Listing (Klein et al. 1982), but for completeness we list them here again in some of the tables. We include into the H-2 complex the cluster of Qa and Tla loci, which we consider as class I loci (Klein et al. 1983). The genetic map of the definitely established loci appears in Figure 1 and is based on the recent results of molecular genetics studies (Steinmetz et al. 1982 a, b). For historical reasons we also describe loci (regions, subregions) that were once thought to be part of the H-2 complex but either they have since been withdrawn, or their actual existence is at present uncertain. We first list loci (regions, subregions) that have been designated by capital letters (we call it Madman's Alphabet because of the frivolity with which symbols have been introduced and then withdrawn again), and then other loci believed to be associated with the H-2 complex. As in the First Listing (Klein et al. 1978), the core of the review in the Second Listing constitutes the tables of H-2 haplotypes, antigens, and determinants.

Animals↗
PubMed1983

Polymorphism of minor histocompatibility genes in wild mice.

H-2b-restricted cytolytic T lymphocytes (CTL) were generated against H-1, H-3, and H-4 antigens and tested against target cells of F1 hybrids between wild mice and inbred H-2b mice. The congenic strain combinations for the CTL production were such that they tested one allele each at the H-1 and H-4 loci and four alleles at the H-3 locus. Most of the wild mice tested came from Southern Germany, but a few mice came from other European countries and Egypt and Israel. Virtually all wild mice typed as positive with CTL directed against H-3b and H-4b antigens; 32% of the F1 hybrids tested reacted with anti-H-1c CTL and 9% reacted with anti-H-3d CTL. The positive results were not caused by cross-reaction with allogeneic H-2 antigens controlled by the major histocompatibility complex (Mhc) genes of the wild mice. At least some of the H-3 and H-4 antigens detected by the CTL in the F1 hybrid were not identical with antigens of the immunizing strains. These results suggest a relatively low degree of polymorphism of the tested minor H loci in wild mice and further support the notion that minor H loci are unrelated to the Mhc.

Animals↗
PubMed1983

Chronic elevation of brain GABA by gamma-vinyl GABA treatment does not alter the sensitivity of GABAergic or dopaminergic receptors in rat CNS.

Rat brain GABA levels were elevated chronically by daily administration of gamma-vinyl GABA, an enzyme-activated, irreversible inhibitor of GABA:2-oxo-glutarate aminotransferase (GABA-T; EC2.6.1.19). Following various periods of drug treatment and withdrawal, the sensitivity of dopamine and GABA receptors in the CNS was determined by biochemical and behavioral evaluations. In contrast to chronic haloperidol treatment, none of the treatment schedules with gamma-vinyl GABA had any significant effect on parameters such as apomorphine induced locomotor activity, [3H] spiperone binding or dopamine-stimulated adenylate cyclase in the corpus striatum; nor did gamma-vinyl GABA treatment affect [3H] GABA binding or GABA-activated [3H] diazepam binding in the cerebral cortex. Moreover, co-administration of gamma-vinyl GABA and haloperidol did not alter the ability of the neuroleptic to induce supersensitivity in the striatal dopaminergic system. Thus, it appears that, in contrast to reported studies using chronic administration of other less specific GABA-T inhibitors such as gamma-acetylenic GABA, amino-oxyacetic acid and isonicotinic acid hydrazide or direct GABA agonists such as THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c-)-pyridin-3-ol) or kojic amine, gamma-vinyl GABA does not alter the sensitivity of the striatal dopaminergic system.

Adenylyl Cyclases↗
PubMed1983

Sixteen new H-2 haplotypes derived from wild mice.

Wild mice captured in Texas, Scotland, Federal Republic of Germany, Denmark, Spain, Greece, Israel, Egypt, and Chile were mated to inbred strains and through successive backcross matings and H-2 typing lines homozygous for wild-derived H-2, haplotypes were established. The lines, which are neither congenic nor inbred, were then typed with antibodies defining known H-2 alleles at class I and class II loci. In addition, antisera were produced by the immunization of inbred strains with tissues of the new lines. Sixteen of the lines were characterized in this manner. The characterization resulted in the identification of 16 new H-2 haplotypes, 11 new K alleles, 10 new D alleles, and 21 new class I antigenic determinants, most of them of the private type. Most of the haplotypes represent natural recombinants sharing segments of the H-2 complex with previously identified haplotypes. A number of haplotypes are recombinants between the K and the A loci, which in genetic studies have proved difficult to separate. The lines, however, also provide evidence for preservation of blocks of genes in the H-2 complex, particularly in the class II region. Some of class I alleles previously found in wild mice from Michigan have now been found again in these mice. Several class II alleles of these lines appear to be the same as those found in inbred strains. Identical or nearly identical class I and class II alleles thus commonly occur in different populations. These findings strengthen the argument that in populations, H-2 alleles are relatively stable.

Animals↗
PubMed1983

Evidence for two suppressor factors secreted by a single cell suggests a solution to the J-locus paradox.

The hybridoma produced by the fusion of lactate dehydrogenase-B (LDH-B)-primed B10.A(2R) mouse suppressor T (Ts) cells with the BW5147 thymoma secretes two kinds of T suppressor factors (TsF), TsF-A and TsF-E. The TsF-A suppresses A beta-restricted and the TsF-E, E beta-restricted helper T (Th) cells. Each of the two factors consists of two polypeptide chains, an antigen-binding chain (ABC) and a major histocompatibility complex (MHC) chain. The ABC binds LDH-B, which is then recognized by one of the two receptors of the Th cell and an antigen bridge is formed between the factor and the Th cell. This chain is presumably identical in both factors. The MHC chain of the TsF-A carries antigenic determinants recognized by three sets of monoclonal antibodies: antibodies specific for the A beta chain, antibodies specific for class II determinants expressed in T cells and controlled by the A beta-E beta chromosomal segment, and antibodies crossreacting with J determinants. The MHC chain of the TsF-E carries determinants recognized by E beta-specific and by J-specific antibodies. Only some of these serologically detectable determinants reside in the region of the TsF molecule recognized by Th cells. These findings suggest that the J determinants are carried by the modified E beta and also by the modified A beta chains.

Animals↗
PubMed1983

Crossreactivity between Qa-1 region and H-2K antigens.

Antiserum (A.TL X A.SW)F1 anti-A.TH is specific for the products of the Qa-1a region. It reacts only weakly or, under certain circumstances, not at all with the immunizing cells, but it reacts strongly with 100% of H-2f and H-2p lymphocytes. The molecules that are the target of this strong heteroclitic reactivity are controlled by a gene in the K region, most likely the K locus itself. The results are interpreted in terms of crossreactivity of Qa-1-specific antibodies with Class I major histocompatibility complex molecules. This crossreactivity underscores the relatedness of Qa and Class I loci and strengthens the argument that Qa loci are members of the Class I family.

Animals↗
PubMed1983

Antigenic drift in visna: virus variation during long-term infection of Icelandic sheep.

A group of 20 Icelandic sheep were infected intracerebrally with visna virus strain 1514, and 209 virus isolates were obtained from the blood, cerebrospinal fluid, and central nervous system (CNS) over a period of 7 years, during which eight animals developed clinical signs of visna necessitating sacrifice. (i) Using type-specific antisera, it was found that 12 (16%) of 76 isolates tested escaped neutralization. These 12 variant viruses were distributed randomly among animals and over time, and did not replace the infecting strain even though all sheep developed homotypic antibody within 3 months of infection. The one exception was sheep no. 1557 (an animal without clinical visna), where the last six isolates were variants. (ii) A total of 35 blood and CNS isolates from seven of these sheep (including five with clinical visna) were tested against serial samples of their own sera. Autologous antisera neutralized all isolates tested with the exception of isolates from sheep 1557. None of the isolates obtained at sacrifice from the five sheep with clinical visna escaped neutralization with autologous antisera. These data suggest that although variant viruses are encountered at considerable frequency during long-term infection of Icelandic sheep, the variants usually do not replace the infecting strain. Antigenic drift does not appear to be essential for virus persistence or for the development of clinically evident CNS lesions.

Animals↗
PubMed1983

Lyt-phenotype conversion of cytotoxic T lymphocytes specific for the A and E class II major histocompatibility complex molecules.

The Lyt-1+ (high) Lyt-2+/- (low) primary cytotoxic T lymphocytes (CTL) specific for A(A alpha A beta) molecules and the Lyt-1+Lyt-2+ primary E(E alpha E beta)-specific CTL are both shown to become Lyt-1 Lyt-2+ effector cells after secondary in vitro stimulation. Thus CTL specific for class II major histocompatibility complex molecules exhibit the same Lyt-phenotype shift as class-I-specific CTL do. The data suggest that either both class-I-specific and class-II-specific CTL follow the same differentiation pathway or regulatory cellular interactions allow only Lyt-1-Lyt-2+ cells to differentiate to secondary CTL.

Animals↗
PubMed1983

Residual minor histocompatibility genes contaminate the B10.AM congenic line: no evidence of C-region-controlled histoincompatibility.

After being primed in vivo and restimulated in vitro, cytolytic T lymphocytes (CTL) were produced in the strain combinations B10.AM anti-B10.A(1R) and B10.A(1R) anti-B10.AM. Although the two strains differ in the chromosomal interval between the E alpha and the D loci, the CTL are not directed against antigens controlled by loci in this interval. Instead, the CTL detect minor histocompatibility (H) antigens controlled by loci that are not linked to H-2. The recognition of the antigens detected by the B10.AM anti-B10.A(1R) CTL is restricted by the Kk and Db molecules, but the CTL also cross-react with the Dd molecule (or a molecule controlled by a locus closely linked to Dd). The recognition of the antigens detected by these two CTL behave as if controlled by alleles at the same minor H locus or loci. This locus is distinct from H-2, and the B10.AM congenic line apparently retained a C3H-derived allele at this locus.

Alleles↗
PubMed1983

H-2 haplotypes carrying identical D but different L alleles.

The B10.SAA48 congenic line was derived by transferring the H-2 haplotype of a wild mouse onto the background of the inbred strain C57BL/10Sn (abbreviated as B10). The line carries the Dw3 allele in combination with an L allele different from that present in other Dw3 strains. One possible explanation of this finding is that crossing over occurred between the D and L loci. The determinants H-2.m64 and H-2.m65 represent an inclusion doublet in which the latter never occurs without the former. Typing of B10.W lines with Ld-specific CTLs reveals the absence of this allele in all the lines, including those carrying an allele serologically similar to Ld.

Alleles↗
PubMed1983

Polymorphism of Qa and Tla loci of the mouse.

Congenic lines carrying H-2 haplotypes derived from wild mice were typed serologically with polyclonal and monoclonal antibodies specific for Tla, Qa-1, and Qa-2 antigens. The typing revealed the presence of a minimum of five Tla, four Qa-1, and three Qa-2 alleles in the 32 lines. Two new Tla, two new Qa-1, and one new Qa-2 alleles could be described. This polymorphism of Tla and Qa loci is lower than that detected at the K and D loci in the same lines. The serological typing for Qa-2 antigens correlates remarkably well with previously published results of typing with cytolytic T lymphocytes. This correlation supports the identify of loci detected by the two methods.

Animals↗