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H Festenstein

Publications and source records attributed to H Festenstein.

At least 109 records · Page 6Linked to original sources

Strong histocompatibility and cell-mediated cytotoxic effects of a single Mls difference demonstrated using a new congenic mouse strain.

In vivo and in vitro effects of incompatibility at the Mls locus have been studied utilizing a recently created congenic mouse strain. Results obtained with skin grafts were compared to those obtained in the mixed lymphocyte reaction (MLR) and cell-mediated cytotoxicity assays. The in vitro responsiveness of cells from skin-grafted mice was compared to that of cells from corresponding ungrafted mice. The results showed that: (a) Mlsa, strongly stimulatory in primary MLR, has a weak effect on skin graft rejection; specific in vivo preimmunization against Mlsa increases and accelerates the rejection of skin grafts, but abrogates the responsiveness in MLR; and (b) incompatibility for Mlsb, nonstimulatory in primary MLR, induces relatively rapid rejection of 100% of skin grafts; this rejection is dramatically accelerated by specific in vivo preimmunization and is followed by activation of helper and cytotoxic cells. Results obtained in the cell-mediated cytotoxicity assay suggest that the recognition of Mlsb determinants is H-2-restricted. Finally, the rejection of skin grafts incompatible for numerous non-H-2 loci is delayed by an additional incompatibility for Mlsb, suggesting that Mlsb decreases the response to other non-H-2 antigens, thus acting as a suppressor and/or competitor antigen. We conclude that, in contrast with previous findings, Mls incompatibility may have a strong effect on skin graft rejection, depending on the allelic combination involved, and, after in vivo immunization, Mlsb activates cell-mediated proliferative and cytotoxic responses and definitely is not "silent". The importance of the histocompatibility effects of Mls determinants and the variety of its biological functions are much in favor of the existence of a polymorphic and complex system capable of activating different cell subsets.

Animals↗

A family study of HLA antigens and other genetic markers in schizophrenia.

HLA antigens and 19 other genetic marker systems were studied in 12 families containing 2 or more members diagnosed as schizophrenic. In contrast with previous reports we could exclude linkage between the disorder and HLA, and we found no evidence of linkage with Gm or Gc. The disagreement between our results and those of a previous study, which suggested linkage between HLA and schizophrenia, could not be explained on the basis of genetic heterogeneity within the disorder. The problems of performing a linkage study in the face of diagnostic uncertainty and an unknown mode of inheritance of the main trait are discussed, and the measures taken in attempts to overcome these difficulties are described. Despite present drawbacks, genetic marker studies hold future promise as a means of detecting major gene effects in schizophrenia and other familial psychiatric disorders.

Female↗

HLA-DB3: population distribution and family studies of a new HLA-D antigen associated with HLA-D antigen associated with HLA-DR4 in Caucasoids.

On the basis of studies with 6 HTCs in four different families the new cluster DB3 identified in the 8th Workshop can be considered an established specificity of the HLA-D series. In 112 healthy Caucasoids resident in South East England the frequency of this antigen was 2.6% similar to the frequency found in 142 Caucasoid patients with rheumatoid arthritis. The frequency in 54 unrelated Chinese individuals from Shanghai and of 120 Nigerians was 7.5% and 3%, respectively. All Caucasoid individuals who were DB3 were also DR4 whereas no such association was found in the two other population groups.

Asian People↗

Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes.

Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.

Animals↗

Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia.

AKR leukemia cell lines differing in the amount of H-2K and H-2D antigens expressed on the cell surface were used to assess cell-mediated immune responses in syngeneic mice against Gross/AKR murine leukemia virus (MuLV)-induced tumors. Leukemic cells with reduced expression of H-2Kk antigens were inactive as inducers of Gross-MuLV/H-2k-specific cytotoxic T lymphocytes (CTL) and resistant to lysis by CTL raised against H-2Kk positive AKR leukemia cells. H-2Kk positive leukemias induced cytotoxic effectors, which upon restimulation in vitro, lysed the stimulating and other H-2Kk positive leukemia cells. In antibody inhibition experiments, T-cell-mediated cytotoxicity to these leukemias could only be inhibited by antisera and monoclonal antibodies specific for the H-2Kk antigens. Due to this specific role of H-2Kk antigens in T-cell cytotoxicity to Gross/AKR MuLV-induced tumors, reduced expression of H-2Kk antigens on spontaneous AKR leukemic cells could have important implications for surveillance of these neoplastic cells.

AKR murine leukemia virus↗

Dominant allele-specific regulation of expression of H-2Kk gene products revealed by somatic cell hybridization.

A study has been made of the H-2 profiles of the AKR thymoma K36 and two series of somatic cell hybrids derived from it. Despite expressing good amounts of the H-2Dk product, the H-2Kk antigen was barely detectable in this tumor, approximately only 1% of that expressed by a comparable AKR lymphoma, 339. The isoelectric focusing profile of the H-2kk product immunoprecipitated from K36 was found to be identical to that from normal AKR lymphocytes. The phenotype of K36 therefore results from regulatory constraints. Fusion of K36 with normal K-2k lymphocytes resulted in hybrids expressing the H-2Kk product. Fusion of K36 with normal H-2b lymphocytes resulted in good expression of the H-2Dk and H-2Db alleles in addition to good expression of the H-2Kb products. The expression of the H-2Kk antigen remained marginal. The data suggest a suppressive mechanism which is trans-acting and dominant and specific for the H-2Kk allele.

Alleles↗

Di-allelic alloantigenic systems on subsets of T cells.

Sera obtained from multiparous women and some of other origin contain antibodies which react with antigens on T cell subsets. These antibodies recognize two distinct diallelic systems, one of which is mainly present on T gamma cells while the other is present on T mu cells. The sera that reacted with the T gamma cells formed a pattern consistent with that of a diallelic system which we have called TCA system with alleles TCA 1 and TCA 2; the sera which reacted with the T mu cells formed a pattern consistent with another diallelic system, independent from TCA, which we have designated the TCB system, with alleles TCB 1 and TCB 2.

Alleles↗

HLA antigen associations in hypertrophic cardiomyopathy.

Histocompatibility antigen testing has been carried out in 20 unrelated normotensive English Caucasoids with hypertrophic cardiomyopathy and in 17 relatives, six of whom also had the disease. A strong association with the HLA-DRw6 antigen complex was found (P = 0.0036) but it was no longer significant after correction for the 52 antigens tested (P = 0.1701).

Adolescent↗

Immunological cross-reactivity between H-2Dk product and DTIC-treated H-2d lymphoma.

The experiments reported here concern the characterization by techniques of in vitro cell-mediated immunity of the antigens induced by 5-(3,3' dimethyl-1-triazine)-imidazole-4-carboxamide (DTIC) on L1210, a chemically-induced lymphoma of DBA/2 mice (H-2d). This series of experiments with the DTIC-treated L1210 tumour show the presence of an 'H-2D'-like antigen which resembles the Dk gene product/s of the H-2k haplotype.

Animals↗

Variation of expression of histocompatibility antigens on tumor cells: absence of H-2Kk-gene products from a gross-virus-induced leukemia in BALB.K.

The antigenic profile of the K-GV tumor of BALB.K origin, induced by Gross virus and maintained in vitro and in vivo, was investigated by serological and immunochemical methods and techniques of cell-mediated immunity. The H-2Kk-gene products were absent by several criteria: (1) monoclonal antibody and conventional alloantisera directed against eh H-2Kk antigenic specificities were nonreactive by direct testing and by absorptions. (2) H-2Kk products could not be precipitated from glycoprotein or protein extracts of the radiolabeled K-GV tumor. (3) Cytotoxic effectors against H-2Kk produced by sensitization in vitro and in vivo failed to kill K-GV target cells. (4) The tumor could neither stimulate BALB.B congenic mice to produce cytotoxic effectors nor specific cytotoxic antibody against H-2Kk-gene products. In contrast, the H-2Dk antigen was readily detectable by all these criteria. These findings therefore describe a tumor which has selectively lost the H-2K-gene products. The K-GV tumor was able to generate Gross-virus specific CTL, but had greatly reduced susceptibility to lysis by Gross-virus specific CTL generated by H-2K expressing AKR (H-2k) tumors. These findings have important implications for the associative recognition of tumor antigens and the immune surveillance of virally induced tumors.

AKR murine leukemia virus↗

Interspecies exchange of beta 2-microglobulin and associated MHC and differentiation antigens.

Radiolabeled human beta 2-microglobulin (beta 2m) can bind to mouse histocompatibility (H-2) antigens on the cell surface or to partially purified H-2 antigens in solution. The complexes containing human beta 2m and H-2 antigens from C3H (H-2k) mice could be immunoprecipitated specifically with alloantisera, rabbit anti-H-2 xenoantisera, and with monoclonal H-2-specific antibodies. Specific association with H-2 antigens was also observed with other haplotypes. The only exception was B10.D2 (H-2d) from which complexes containing human beta 2m could only be precipitated with anti-H-2-xenosera. Thus radiolabeled human beta 2m can be used as a specific label for mouse H-2 antigens in precipitation and radioimmunoassays. The application of this finding extends to major histocompatibility complex antigens of other species, and to differentiation antigens with primary association with beta 2m.

Animals↗