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J Klein

Publications and source records attributed to J Klein.

At least 793 records · Page 44Linked to original sources
PubMed1982

Serological and biochemical characterization of class II antigens in B10.W lines.

Class II molecules of 17 B10.W lines (i.e., congenic lines carrying H-2 haplotypes of wild mice on C57BL/10Sn or B10 strain background) were analyzed by immunochemical methods of precipitation and co-precipitation. The analysis included typing for previously defined antigenic determinants, as well as determinants defined by new reagents, and mapping of the genes controlling these determinants. Using this approach, an Ia chart of the typed B10.W lines could be constructed. Genes controlling determinants Ia.38, 102, 103, 104, 105, and 106 were mapped into A (A beta or A alpha) locus; genes controlling determinants Ia.41. 107. 108, and 109 were mapped in the E (E beta or E alpha) locus. The study suggests that the polymorphism of at least some of the class II loci could be as high as that of the class I loci.

Animals↗
PubMed1982

Haplotype-specific suppression of T cell response to lactate dehydrogenase B in (responder x nonresponder)F1 mice.

Mouse strains that express the Ek (Ek beta E-1k alpha) molecule are nonresponders (NR) to the enzyme lactate dehydrogenase B (LDHB) in terms of T cell proliferation. Nonresponsiveness is caused by T suppressor (Ts) cells recognizing LDHB in the context of Ek molecules on the antigen-presenting cells. The data presented here demonstrate that the Ek-restricted Ts cells function in (R x NR)F1 mice in a remarkable haplotype-specific fashion: they selectively interfere with the Ak (ANR)-restricted response, and do not affect the response channeled through the A molecules of the responder parent. This haplotype-specificity of suppression provides an explanation of the dominance of responsiveness in (R x NR)F1 mice.

Animals↗
PubMed1982

Evidence for placing the Neu-1 locus within the mouse H-2 complex.

Congenic lines B10.KPA42, B10.KPA132, B10.SNA57, B10.DRB62, and B10.WOA105 carry H-2 haplotypes of wild mice on the genetic background of the strain C57BL/10Sn. Two of the lines (B10.DRB62 and B10.WOA105) have H-2 haplotypes indistinguishable from H-2v of B10.SM. The H-2 haplotype of one line (B10.SNA57) seems to have arisen from H-2v by recombination between the D and Qa-2 loci. The H-2 haplotypes of the remaining two lines probably arose from H-2v by recombination between the C4 and D loci. Since all six and no other lines carry the rare Neu-1a allele, the neuraminidase-1 locus is probably located proximal to the H-2D locus. Typing of H-2s recombinants for the enzyme acid phosphatase liver, the processing of which is controlled by the Neu-1 locus, suggests that the locus resides between the E alpha and D loci, that is in the S region.

Acid Phosphatase↗
PubMed1981

Endogenous GABA determines the characteristics of [3H]GABA-binding.

Since the identification of sodium-independent GABA-binding sites in membrane preparations from the mammalian central nervous system numerous publications have dealt with the effects of putative endogenous inhibitors of GABA-binding. However, controversy has arisen over the existence and identity of such inhibitors and the possible artifactural role of residual endogenous GABA in the interpretation of GABA-binding data. Using direct determination of GABA concentrations we have demonstrated that it is extremely difficult to remove endogenous GABA from rat brain membrane preparations and have shown that, even in well-washed preparations, there is a source of GABA production which compounds this problem. When care has been taken to ensure that GABA concentrations are minimal, analysis of binding data reveals the presence of two classes of GABA-binding sites with dissociation constants of the order of 9 nM and 318 nM and maximum binding capacities of 0.63 and 1.65 pmol/mg protein respectively (i.e., 63 and 165 pmol/g original wet tissue). A theoretical analysis of the effects of endogenous GABA demonstrates how failure to take into account even very low concentrations of GABA leads to misinterpretation of the results.

Animals↗
PubMed1981

Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains.

T cells from strains responder to the antigen poly(Glu40 Ala60) (GA) were depleted of alloreactive cells by bromo-deoxyuridine and light treatment, and were subsequently primed in vitro in GA presented by allogeneic macrophages from nonresponder strains. Antigen-specific secondary proliferative responses restricted by allogeneic Ia molecules of the macrophages were obtained in all strain combinations tested. These data indicate that Ir gene-controlled nonresponsiveness cannot be the result of a failure of antigen presentation.

Animals↗
PubMed1981

The traditional and a new version of the mouse H-2 complex.

The H-2 complex has traditionally been interpreted as a maze of regions, subregions and loci coding for different traits. The two main theses presented here are, first, that a single H-2 locus is pleiomorphic in that it controls several functions such as allograft rejection, cell-mediated lymphocytotoxicity, mixed lymphocyte reaction, immune response, immune suppression and restriction of T-cell specificity; and second, that the physiological function of the H-2 complex is to guide T lymphocytes in their function of distinguishing self from non-self, and that all other H-2-controlled traits are artificial derivatives of this basic function. These two theses lead to a new, simplified interpretation of the H-2 complex.

Alleles↗
PubMed1981

Detection of CML determinants associated with H-2 controlled E beta and E alpha chains.

The serologically detectable molecules encoded by the H-2 complex, the major histocompatibility complex (MHC) of the mouse, fall into two classes-class I and class II (ref. 1). The class I molecules encoded by the K and D loci have a molecular weight of 44,000 and are noncovalently associated with beta 2 microglobulin which is not controlled by the MHC. The class II molecules are of two kinds, A and E, each consisting of two noncovalently associated polypeptide chains, alpha (Mr approximately 34,000) and beta (Mr approximately 28,000). Three of the four chains, A alpha, A beta and E beta, are controlled by loci in the I-A subregion, whereas the locus controlling the E alpha chain is located in the I-E subregion of the H-2 complex. Thus the loci coding for the E alpha and E beta chains are separated by at least one (J) and perhaps more loci. It has been shown that the E alpha and E beta chains are synthesized independently, and that the E alpha chain is required for the insertion of the E beta chain in the plasma membrane. We demonstrate here that the E alpha E beta complex (the E molecule) can evoke in vitro cell-mediated lymphocytotoxicity (CML) without previous sensitization in vivo, and that the strong CML reactivity is directed against allele-specific determinants on the highly polymorphic E beta chain.

Alleles↗
PubMed1981

Terminal differentiation of T cells specific for mutant H-2K antigens. Conversion of Lyt-1,2 cell into Lyt-2 but not Lyt-1 cells, in vitro.

The Lyt phenotype of T cells at different stages of response to mutant H-2K antigens was determined by immunofluorescence using monoclonal rat anti-Lyt antibodies. Previous observations indicated a differential expression of the two allelic forms of Lyt-1 antigen on these cells. Since the rat antibodies recognize nonpolymorphic framework determinants of Lyt antigens, in our approach the expression of both Lyt-1 alleles was analyzed with the same antibody. It was found that cells reacting to three different H-2K mutants have the Lyt-1,2 phenotype, regardless of the Lyt-1 allele carried by the responder strain. The Lyt phenotype of responder cells remained unchanged after priming in vivo. However, cells recovered from cultures after secondary stimulation in vitro were mainly Lyt-2, with few Lyt-1,2 and virtually no Lyt-1 cells present. This change of Lyt phenotype ran in parallel with the loss of proliferative capacity to the priming antigen, but cytolytic activity of the cells remained unimpaired. Long-term proliferation of T cells induced against mutant H-2K antigens could only be maintained in the presence of a T cell growth factor. Cultures with growth factor contained almost exclusively Lyt-2 cells and exerted strong cytolytic activity. These results demonstrate that the Lyt differentiation pathway of anti-mutant T cells is from Lyt-1,2 to Lyt-2. Furthermore, the data suggest that no helper cells are induced in response to mutant H-2K antigens. A model which incorporates these findings into current concepts of T cell differentiation is discussed.

Animals↗
PubMed1981

Lyt phenotypes of primary cytotoxic T cells generated across the A and E region of the H-2 complex.

Six different cell-mediated lympholysis (CML) combinations were established, four of which generated effector cells against the I-E, and two against the I-A molecule. The cell surface phenotype of effector cells was then determined by depletion of cytotoxic T lymphocyte (CTL) activity with antisera and rabbit complement (C) treatment. Both types of effector cells were completely eliminated by treatment with anti-Thy-1.2 antiserum plus C. Anti-Lyt-1.2 and C depleted anti-A and anti-E killer activity but did not eliminate CTL generated across a whole H-2 difference. One out of three different batches of anti-Lyt-2.2 antiserum did not deplete anti-A killer activity, while it efficiently eliminated CTL generated across the E region or whole H-2 difference. However, two batches of anti-Lyt-2.2 antiserum depleted also anti-A CTL activity. A quantitative difference between anti-A and anti-E CTL in terms of Lyt-2 expression was demonstrated by significant differences in recovery of killer activity, after treatment of these two types of CTL with a wide concentration range of the same anti-Lyt-2.2 antiserum and C. Thus it is concluded that anti-A killer cells have the cell surface phenotype of Thy-1+, Lyt-1, Lyt-2, whereas anti-E CTL are Thy-1+, Lyt-1, Lyt-2. The data are discussed in the context of a possible association of Lyt phenotypes of T cells with the type of MHC antigens they recognize.

Animals↗
PubMed1981

Mouse mitochondrial superoxide dismutase locus is on chromosome 17.

The hamster X mouse hybridoma cell line GCL28 carries only one copy of mouse chromosome 17 but expresses H-2 antigens controlled by the major histocompatibility complex of the mouse. The cell line and clones derived from it were subjected to treatment with H-2 specific antisera and complement and a series of H-2 antigen-negative clones was produced. Typing of the clones for the mouse enzyme glyoxalase 1, which is encoded by an H-2-linked gene, revealed that the loss of H-2 antigen expression was accompanied by the loss of chromosomes 17 in these clones. This suggestion was verified by karyotype analysis of selected clones. Typing of the clones and subclones for the mouse mitochondrial superoxide dismutase (SOD-2) indicated complete concordance between loss of chromosome 17 and loss of SOD-2 activity. This finding suggests that the locus controlling the expression of SOD-2 is located on chromosome 17. Since a similar locus in the human is linked to HLA, the human major histocompatibility complex, extensive homology must exist between the mouse and human MHC-bearing chromosomes.

Animals↗
PubMed1981

An H-2 haplotype possibly derived by crossing-over between (A alpha A beta) duplex and the E beta locus.

The B10.STA62 strain carries the H-2w27 haplotype derived from a wild mouse captured in the vicinity of Ann Arbor, Michigan. Products of two class II loci composing this haplotype, A alpha and A beta, are serologically, biochemically (by tryptic peptide mapping), and functionally indistinguishable from products controlled by the Ab alpha and Ab beta genes of the B10.A(5R) strain. In contrast, the polypeptide chain controlled by the third class II locus, E beta, is different from that controlled by the Eb beta gene. This Ew27 beta chain lacks an antigenic determinant present on the Eb molecule and carries determinants lacking on the Eb molecule, the Eb beta and Ew27 beta peptide maps differ in at least six peptides, and cytotoxic T cells specific for the Eb beta chains do not react with B10.STA62 target cells. This great difference between the Eb beta and Ew27 beta chains suggests that the corresponding genes have not been derived from one another by a direct mutational conversion; instead, H-2w27 appears to be a recombinant haplotype derived by crossing-over between the A alpha A beta duplex and the E beta locus. This is the first recombinant discovered separating these class II loci.

Animal Population Groups↗
PubMed1981

Generation of cytotoxic T lymphocytes by the H-2-encoded E molecules.

Primary CML was generated in strain combinations 4R anti-2R, R107 anti-3R, 7R anti-9R, and GD anti-R101-combinations differing only in the chromosomal interval between the I-A subregion and the Ss locus. No CML could be obtained in any of the reciprocal combinations of these strains. This unidirectionality of the CML reaction correlates with the expression or nonexpression of the E molecules encoded by this interval: the reaction occurred in combinations in which the responder strain lacked and the stimulator strain expressed the E molecules in the cell membrane. The CML reaction was positive when tested on LPS-stimulated blast cells but weak on Con A-stimulated blasts and negative on Ia-negative tumor cells. The reaction could partially be inhibited by monoclonal antibodies to the Ia.m7 determinant presumably carried gy the E alpha chain; it was not inhibited by monoclonal antibodies specific for Ia determinants carried by the A molecule. Cytotoxic lymphocytes specific for a particular combination of E beta and E alpha chains reacted with all cells expressing the particular E beta chain, no matter what the origin of the E alpha chain associated with the E beta chain was. Attempts to generate cytotoxic lymphocytes specifically reactive with allotypic determinants on E alpha chains failed. In F1 hybrids expressing one type of E alpha chain and two types of E beta chain, the single E alpha chain was found to associate with both beta chains, producing two types of E molecule. We conclude from these experiments that the CML determinants detected in the strain combinations used are encoded by the same loci as those coding for the serologically detectable Ia determinants. The CML determinants are carried by the E beta chains; the E alpha chain does not contribute in any way to the specificity of determinant recognition by the cytotoxic lymphocytes. No evidence for allotypic variation of the E alpha chain as detected by the CML assay could be found in this study.

Animals↗