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Biomedical subjects

W Bodmer

Publications and source records attributed to W Bodmer.

At least 55 records · Page 3Linked to original sources

Monoclonal antibodies to HLA-DP-transfected mouse L cells.

Mouse L cells transfected with human HLA-DP (DPw4) alpha and beta genes were used to make monoclonal antibodies in C3H mice. A polymorphic antibody, DP11.1, was obtained, as well as several monomorphic antibodies. In ELISAs, DP11.1 bound to DPw4 cells and, more weakly, to DPw2, but not DPw1, -3, -5, or -6, using HLA homozygous cells. It also bound to L-cell transfectants expressing either DPw2 or DPw4 products. From B lymphoblastoid cell lysates labeled with [35S]methionine, the antibody immunoprecipitated alpha and beta chains of a similar size to those precipitated by a well-characterized DP monoclonal antibody, B7/21.2. Immunoblotting indicated that the DP11.1 antibody was directed against the alpha chain. This result confirms partial sequence data that showed that the DP alpha chain, as well as DP beta, is polymorphic, and that DPw2 and -4 alpha chains are very similar, if not identical.

Animals↗

Preparation and characterization of monoclonal antibodies against placental alkaline phosphatase and other human trophoblast-associated determinants.

We have prepared monoclonal antibodies by immunizing BALB/c mice with purified human term placental plasma membranes. The antibodies were selected to show predominant specificity for trophoblast and trophoblast derivatives. Four of these antibodies have been found to recognize the placenta-specific isozyme of alkaline phosphatase (EC 3.1.3.1), and to cross-react with the closely related testis form of this enzyme. One antibody recognized transferrin, a serum protein with an abundant placental receptor. The specificities of the other antibodies, whose target antigens are unknown, are described. Their reactivity with some human tumour-derived epithelial cell lines suggests that they may provide useful markers of human trophectoderm differentiation, as well as for properties selected for during tumour progression.

Alkaline Phosphatase↗

Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes.

Three sets of cosmid clones--containing the HLA-DR alpha chain gene and two additional related genes--were isolated from human genomic DNA libraries by using a cDNA probe for the HLA-DR alpha chain. Southern blot analysis using DNA from somatic cell hybrids indicated that all of the clones mapped to chromosome 6. Partial sequence analysis showed that the two additional related genes were highly homologous to each other, and to the HLA-DR alpha chain, in parts of the exon that encoded the alpha 2 domain but were more divergent in intron sequences. One of the genes corresponds to the HLA-DR-related DC series. DNA probes made from this gene revealed marked restriction enzyme polymorphism when hybridized to genomic DNA from HLA-DR typed homozygous cell lines. The patterns obtained from a number of homozygous and heterozygous cell lines correlated with the HLA-DR crossreactive serotypes and also indicated that there is a further sequence in the haploid human genome that is closely homologous with the DC alpha chain sequence. One family was studied and showed the expected HLA-DR-associated inheritance of restriction enzyme patterns. No polymorphism has yet been demonstrated in restriction enzyme fragments that include the other cloned sequence, which may correspond to the SB alpha chain gene or to a novel HLA-DR-related gene. These experiments indicate that there are at least three sequences in the human genome related, but not identical, to the HLA-DR alpha chain gene.

Base Sequence↗

Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers.

Two monoclonal antibodies, 3.14.A3 and 1.10.F3, raised against a delipidated preparation of the human milk fat globule and characterized as epithelium-specific (Taylor-papadimitriou et al., 1981) were assayed histologically, by an indirect immunoperoxidase technique, against formalin-fixed, paraffin-embedded, normal and tumour tissue sections, in order to establish their in vivo specificity. Both antibodies bound to less than 10% of the alveoli and ducts in the resting breast, but bound to all areas of alveoli, ducts and secretion in the lactating breast. Binding was to the luminal surface of the alveolar and ductal epithelium. Antibody 3.14.A3 showed positive reactions with each of 20 primary breast carcinomas tested, and with metastatic lesions in lymph nodes from six of these. Antibody 1.10.F3 also reacted with most of the primary carcinomas but not with those of the mucoid type nor with metastatic lesions in lymph nodes. When tested against a variety of normal tissues, 1.10.F3 bound only to the luminal epithelial surface of classically defined exocrine glands, to their associated ducts and to the collecting tubules of kidney and bronchioles of the lung. 3.14.A3 showed a similar pattern of binding to 1.10.F3 but also bound to sweat glands, the alveolar epithelium of lung and the luminal epithelium of the ductuli efferentes of the epididymis. The only tumours, other than breast, showing a positive reaction with the antibodies were adenocarcinomas of the lung, uterus and ovary.

Antibodies, Monoclonal↗

HLA haplotype associations with disease.

Interest recently has extended to the problem of looking for HLA haplotype associations with particular diseases. Higher order interactions, that is to say of particular haplotypes with a disease, are much more complicated than individual antigen associations, with which most disease studies have so far been concerned. Our aim in this work is to explain the concept of higher order interactions and to discuss the difficulties involved when trying to measure such haplotype associations. The main emphasis is to point out that it is not easily possible to detect haplotype associations if an individual antigen association with the disease exists.

Alleles↗

Serological identification of Ia antigens: report of a British region Ia workshop.

In preparation for the 7th International Histocompatibility Workshop 13 laboratories in the British Region participated in a local workshop. One hundred and twenty-three sera which had been previously shown to have activity on either normal B cells, CLL cells or B cell lymphoid lines in the absence of HLA-A, B or C activity were exchanged between the laboratories. These sera were tested on a total of 212 B cells, 101 CLL cells, 76 T cells and 76 lymphoid cell lines. The data was collected and analyzed in Oxford. The analysis showed that six groups of sera could be distinguished. When these groups were compared with the D locus typing of some of the lymphoid lines which were derived from individuals used as MLC typing cells, they were seen to have significant associations with D locus antigens. The serological groups defined were therefore given numbers corresponding to the D locus numbers they associate with, i.e. UK1 is associated with DW1 and so on for UK2, 3, 4, 5 and 7. Comparison of typing techniques showed that long incubation both with antiserum and then with complement, 1 hour + 2 hours gave the best and most reproducible reactions on normal B cells. Residual anti-HLA-A, B or C activity in some of the sera even after platelet absorption showed the importance of adequate checking on T cells after absorption.

Antibody Specificity↗