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Biomedical subjects

M L Bach

Publications and source records attributed to M L Bach.

At least 37 records · Page 2Linked to original sources

Primed LD typing: reagent preparation and definition of the HLA-D-region antigens.

Primed LD typing cells were prepared against single HLA haplotypes within families and used to type a random panel of 48 individuals. PLT cells could be grouped on the basis of highly correlated responses with the panel test cells; the 21 different PLT cells could be used to define 6 different PL antigens. One of these, PL 3, was split by the responses of two of the 21 PLT cells which measured an antigen called PL 3.1.

Epitopes↗

Lymphoblastoid cell lines of homozygous typing cells used for sensitization in PLT.

Lymphoblastoid cell lines of homozygous typing cells were used as the sensitizing cells in MLC to prepare PLT cells. Results obtained using such cells against a panel of restimulating cells were compared to those obtained using regular PLT cells in which priming had been accomplished with normal peripheral blood lymphocytes. It appears that lymphoblastoid cell lines can be used for this purpose; the advantages of such an approach are given.

Cell Line↗

Three HLA-D region antigens defined by primed LD typing.

We have recently described a new method, primed LD typing or PLT, for specific identification of HLA-D antigens. Highly discriminatory PLT cells have been developed which clearly differentiate between cells of individuals that restimulate strongly and those that restimulate weakly. Seven such discriminatory PLT cells have been used to define three antigens called PL1, PL2, and PL3; two more PLT cells may define antigen(s) PL4.

Genes↗

Secondary cell-mediated lympholysis: importance of H-2 LD and SD factors.

Lymphocytes stimulated in mixed leukocyte cultures and left for 13-17 days, i.e. beyond their peak proliferative and cytotoxic reactivities, can be restimulated to give a secondary-type rapid and strong proliferative and cytotoxic response when confronted with cells of the original sensitizing cell donor. We have concerned ourselves primarily with the requirements of restimulation for the presence of LD and/or SD stimuli on the restimulating cells. (a) The low level cell-mediated lympholysis (CML) associated with LD differences in a primary CML can be restimulated to give a secondary-type response by those same LD antigens. (b) If the original sensitizing cells differ from the responding cells by both LD and SD antigens, restimulation with only the LD antigens, or third-party cells presumably carrying cross-reactive LD antigens, can restimulate the secondary CML responses directed against the SD antigens on the original sensitizing cells. (c) The presence of SD antigens on the restimulating cells that are cross-reactive with the primary sensitizing SD antigens (as determined in a primary CML) leads to the preferential activation of cytotoxic T lymphocytes reactive to those antigens although maximum cytotoxicity is still directed at cells carrying the original sensitizing SD antigens. A model to explain these results is presented.

Animals↗

Differential function of major histocompatibility complex antigens in T-lymphocyte activation.

We have emphasised the functional dichotomy of MHC LD and LD antigens as well as the differences in cellular responses to these antigens. Perhaps in so doing we have failed to stress adequately the similarities that exist. But while the similarities (for example skin graft rejection associated with both K and I region differences) are so very clear, the differences have best allowed our progressive understanding of MHC induced cellular responses from the perspective stressed in this article. Of greatest importance to our understanding of these transplantation antigens are the potentially differential roles for the LD and SD antigens in the complex series of events that are collectively referred to as the "allograft reaction". It has been suggested that these differences may be "merely quantitative". This possibility has been discussed repeatedly in our previous reports on the distinction of LD and SD. In fact, the great bulk of biological phenomena can be reduced to quantitative differences. It would seem to us that sufficient evidence for such differential activity exists to make the LD-SD dichotomy model an heuristically valuable one for purposes of designing future experiments. We have discussed the clinical relevance of this model elsewhere. Many authors have speculated and evidence has been gathered to suggest, that cell surface antigens associated with the MHC are important in developmental and other cell interactions. Some studies have directly addressed the question of the need for MHC compatibility to allow cell interaction to proceed optimally. It thus seems most appropriate that the genetic complex with which we are dealing has been termed the major histocompatibility complex; allowing for the literal interpretation of this term this may be the genetic region that by its influence on "tissue compatibility" may control critical cellular interactions in addition to those observed in allograft reactions. It is the simple good fortune for those whose attention was focused on this complex by transplantation problems to find themselves with a panorama of biological phenomena that require extensive experimental probing and integration, hopefully ultimately leading to an understanding of the MHC in a broader context than has to date been possible.

Animals↗

beta2-Microglobulin: a reevaluation.

Rabbit antiserum to human beta2-microglobulin was used to inhibit the proliferative response of lymphocytes in a variety of in vitro assays and to block the effector phase of the cell mediated lympholysis reaction. The antiserum was able to inhibit both of these reactions; it is not clear whether the cytotoxic reaction that we are studying in a xenogeneic human-rabbit system is based on phytohemagglutinin dependent cytotoxicity or on specific recognition of target cells by receptors on the effector cells, or most likely on a combination of both cytotoxic mechanisms. Whereas the possibility that beta2-microglobulin may be associated with receptors on the thymus-derived lymphocyte surface is considered, it is also pointed out that the effect of the antiserum may be based on other mechanisms of perturbing the membrane so as to inhibit these responses.

Antigen-Antibody Reactions↗

HL-A LD (lymphocyte defined) typing: a rapid assay with primed lymphocytes.

When human lymphocytes are cultured for 9 to 14 days with stimulating cells of a family member differing by a single HL-A haplotype they become "primed" to recognize specific HL-A LD (mixed lymphocyte culture) antigens. These primed lymphocytes respond specifically and rapidly when "restimulated" with cells of a person that contain the same LD antigens as those of the priming haplotype. Specific HL-A LD antigens can be detected within 24 hours by this primed LD typing.

Alleles↗

Genetic and cellular control of in vitro models of allograft reactivity.

In each species sufficently studied, a single genetic region, the major histocompatibility complex (MHC), controls the strong transplantation antigens. Recent evidence suggests that the genetic control of differences important in allograft phenomenon is more complex than previously realized. In addition to the two loci, alleles of which control serologically defined (SD) antigens, there are other loci the phenotypic products of which lead to T-lymphocyte activation in mixed leukocyte culture. These latter loci have been referred to as LD (or lymphocyte defined). There appears to be a physiologic interaction between these two loci in that the LD differences seem to be important in the initial recognitive phases of the allograft reaction; the SD differences (or products of genes very closely linked to those determining the SD antigens) are important as a target for cytotoxicity as studied by the cell-mediated lympholysis test.

Animals↗

Genetic aspects of canine mixed leukocyte cultures.

Recent data stress the importance of matching donor and recipient of an organ graft for both the serologically defined (SD) and lymphocyte-defined (LD) determinants. To allow experimental evaluation of the effect of these SD and LD structures in a noninbred experimental animal, mixed leukocyte culture tests were performed between SD identical and nonidentical dogs to clarify the LD system in these animals. The results of these experiments can be summarized as follows: (a) In the dog there is a LD locus distinct from the known SD loci, which in all probability is localized outside the first (SD-1) series locus on the chromosome. (b) The crossing-over frequency between the SD and LD loci on the chromosome is low. (c) Studies in SD identical unrelated dogs and random unrelated dogs show an apparent high linkage disequilibrium between SD and LD loci. (d) The LD system in dogs is polymorphic.

Animals↗

Chloral hydrate: a solvent for biological membranes.

A buffer system conitainin chloral hydrate, taurine, and bromopyridinium lactate was used to dissolve several biological membranes and separate their protein components by polyacrylamide gel electrophoresis. This solvent system was capable of separating molecules of similar size on the hasis of their charge and allows easy recovery of the proteins Thus. aqueous chloral hydrate is an effective solvent for biological membranes.

Animals↗