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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 865 records · Page 48Linked to original sources
PubMed1978

T-lymphocyte response to H-2 mutants. I. Proliferation is dependent on Ly 1+2+ cells.

We have determined the Ly phenotype of the T lymphocytes which proliferate in response to mutant H-2K and H-2D alloantigens in primary mixed lymphocyte culture. Responder T cells proliferating in reciprocal cultures of H-2d(KdDd) and H-2da(KdDda) lymphocytes were typed Ly 2+ through selective depletion with specific alloantiserum plus complement. Further, B6-Ly 1a lymphocytes proliferating in response to B6-H-2ba and B6-H-2bf stimulators were typed as Ly 1+2+ through similar analysis. These results are discussed with regard to their impact on views of lymphocyte differentiation and factors determining the identity of alloreactive lymphocytes.

Animals↗
PubMed1978

Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

Animals↗
PubMed1978

On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?

In the thymus, precursor T cells differentiate recognition structures for self that are specific for the H-2K, D, and I markers expressed by the thymic epithelium. Thus recognition of self-H-2 differentiates independently of the T cells H-2 type and independently of recognition of nonself antigen X. This is readily compatible with dual recognition by T cells but does not formally exclude a single recognition model. These conclusions derive from experiments with bone marrow and thymic chimeras. Irradiated mice reconstituted with bone marrow to form chimeras of (A X B)F1 leads to A type generate virus-specific cytotoxic T cells for infected targets A only. Therefore, the H-2 type of the host determines the H-2-restricted activity of killer T cells alone. In contrast, chimeras made by reconstituting irradiated A mice with adult spleen cells of (A X B)F1 origin generate virus-specific cytotoxic activity for infected A and B targets, suggesting that mature T cells do not change their self-specificity readily. (A X B)F1 leads to (A X C)F1 and (KAIA/DC) leads to (KAIA/DB) irradiation bone marrow chimeras responded against infected A but not B or C targets. This suggests that cytotoxicity is not generated against DC because it is abscent from the host's thymus epithelium and not against DB because it is not expressed by the reconstituting lymphoreticular system. (KBIB/DA) leads to (KCIC/DA) K, I incompatible, or completely H-2 incompatible A leads to B chimeras fail to generate any measurable virus specific cytotoxicity, indicating the necessity for I-specific helper T cells for the generation of killer T cells. Finally adult thymectomized, irradiated and bone marrow reconstituted (A X B)F1 mice, transplanted with an irradiated thymus of A origin, generate virus-specific cytotoxic T cells specific for infected A targets but not for B targets; this result formally demonstrates the crucial role of thymic epithelial cells in the differentiation of anti-self-H-2 specificities of T cells.

Animals↗
PubMed1978

The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help.

The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.

Animals↗
PubMed1978

Buridan's ass: one man's view of the immune system.

This essay offers a highly biased and prejudiced interpretation of the immune response. The major points of this interpretation are: B and T lymphocyte diversity is generated by rearrangements within and among existing receptorcoding genes; the T cell receptor is a molecule genetically more closely related to immunoglobulins than to the products of the major histocompatibility complex (MHC); the course of B and T lymphocyte differentiation is largely the same except for a final processing of T lymphocytes in the thymus; the processing is directed by MHC molecules of the thymus epithelium; Ir and Ia genes are identical; and the function of MHC polymorphism is to generate diversity at the population level.

Animals↗
PubMed1978

Localization of mouse Pgk-2 gene at the D end of the H-2 complex (1).

A survey of the Pgk-2 alleles carried by H-2 congenic lines of mice has established that the Pgk-2 locus is near the D end of the H-2 complex on chromosome 17. A comparison among inbred strains of the alleles for Pgk-2, H-2, and two other genes in this vicinity, Tla and Ce-2, has revealed a remarkable correlation suggestive of strong linkage disequilibrium in the wild mice from which the inbred strains were derived.

Alleles↗
PubMed1978

[Genetic linkage of HLA-Bf. Study of 19 informative families].

Since the discovery of the linkage between HLA and Bf by Allen in 1974 several reports have shown a very close linkage between Bf and HLA-B. We have studied 19 families with 81 offsprings for the linkage between HLA (A,B) and Bf. The total "lod scores" in our material for the linkage between HLA-B and Bf is 17,167 at theta = 0.00. No recombination was observed between HLA-B and Bf. One recombination out of 79 informative meiotic divisions was observed between HLA-A and Bf. This result would mean that the Bf locus is about 1.3% recombination fraction far from the HLA-A locus. Our estimation is in good agreement with the results of other authors. However the estimation of recombination fractions is only an arbitrary mean to map genetic loci on chromosomal regions and family studies of cases with intra-HLA cross-overs are of more interest. All available data from the litterature are in favour to a very close linkage between Bf and HLA-B and to a situation of the Bf locus between HLA-B and HLA-D. However some conflicting data on Bf gene mapping have been published. More precise informations may be obtained as soon as a more exact structure of the HLA region, in particular of the HLA-D region, will be known.

Adult↗
PubMed1978

Cerebrospinal fluid acid-base balance during muscular exercise.

Ventilation, metabolism, arterial blood gases, and blood and cerebrospinal fluid (CSF) acid-base status were measured in exercise studies on seven ponies during mild, moderate, and near-maximal treadmill exercise. CSF and arterial blood were sampled via indwelling catheters. Generally measurements were made during the 3rd, 6th, and 9th minute of steady-state exercise, with CSF sampled only during the 9th minute. Alveolar ventilation (VA) and metabolic rate (VO2) increased proportionately during exercise below the anaerobic threshold, but above this threshold, VA increased at a faster rate than VO2. The similarity of these response to those observed in man suggests the pony is a suitable animal model for study of exercise hyperpnea. No change in CSF acid-base balance occurred with light-to-moderate work; however, with near-maximal work a fall in CSF carbon dioxide partial pressure due to hyperventilation caused CSF to become alkaline (pH = 7.380) relative to rest (pH = 7.330). CSF lactate increased slightly with exercise but had no effect on CSF [HCO3-], which remained constant from rest to severe exercise. We conclude that it is unlikely the hyperpnea at any intensity of exercise results from an increased H+ stimulation at the medullary chemoreceptor.

Acid-Base Equilibrium↗
PubMed1978

The unity of genes in the major histocompatibility complex.

The major histocompatibility complex (MHC) of the mouse can be genetically divided into several regions specialized to performing specific functions. Thus the class I regions (K and D) code for antigens that activate effector (killer) T cells, class II region (I) for antigens causing T-cell proliferation, and class III regions (s) for complement components. A strong case is made for the theory that the division of labor within the MHC is not absolute. Evidence is presented that class I antigens can sometimes cause as strong T-cell proliferation as class II antigens; that class II antigens can generate effector T cells; and that class I antigens may be involved in the immune response to some antigens. The fact that different regions can perform similar functions argues for the unity of the MHC genes.

Animals↗
PubMed1978

Structural studies on protein products of murine chromosome 17. III. Partial amino acid sequence of an H-2Kq molecule.

Twenty-one of the amino terminal twenty-seven amino acid residues have been assigned in the murine H-2Kq molecule and several additional assignments and corrections have been made in both the H-2Kk and H-2Kb molecules. The study shows that 1) H-2Kk and H-Kq, which are serologically related, have an identical amino acid sequence for all twenty positions that can be compared, 2) the H-2Kk and H-2Kq molecules differ from H-2Kb at only two positions--9 and 22, and 3) the additional sequence data on the H-2Kk, -Kb, and -Kq molecules increases the already striking homology between murine and human transplantation antigens.

Amino Acid Sequence↗