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J Bodmer

Publications and source records attributed to J Bodmer.

14 recordsLinked to original sources
PubMed1989

Molecular analysis of the HLA-DR5 haplotype.

A panel of eleven HLA-DR5 homozygous lymphoblastoid cell lines was investigated for structural heterogeneity on the product level. HLA class II antigens were isolated by immunoprecipitation with different anti-class II monoclonal antibodies and separated by two-dimensional (2-D) gel electrophoresis. As a result, three distinct DRB1, one commonly expressed DRB3, and two distinct DQ gene products could be identified that combined to four different haplotypes associated with HLA-DR5. A hitherto serologically undetected split of HLA-DRw11 was presented by three cell lines. HLA-DRw11 and HLA-DRw12 were found to be related allospecifities that differ only in their DRB1 locus products, but are closely associated with the supertypic DRB3 allele HLA-DRw52b and with HLA-DQw7. The DRB3 alleles HLA-DRw52a and DRw52c were not detected in our cell line panel, indicating that these supertypic determinants are in negative linkage disequilibrium with HLA-DR5. Our data suggest that intra HLA-DR/DQ crossing-over events contribute to the development of the HLA class II polymorphism. Evidence is presented that the T cell defined HLA-D allospecifities are commonly determined by DRB1 and DQ gene products.

Amino Acids↗
PubMed1988

HLA-D region alpha-chain monoclonal antibodies: cross-reaction between an anti-DP alpha-chain antibody and smooth muscle.

Two monoclonal antibodies, Tal 3C3 and Tal 1B5, raised against purified plasma membrane extract of the Bristol 8 B lymphoblastoid cell line and previously shown to recognize epitopes on denatured HLA-D alpha-chains revealed several differences in staining patterns when screened by immunocytochemical techniques on pre-fixed paraffin-embedded sections of human tissues. Although Tal 3C3 staining was weaker and more restricted than Tal 1B5 on immunoregulatory cells expected to express class II antigens, this monoclonal antibody showed additional strong activity on normal smooth muscle. Biochemical studies show that whereas Tal 1B5 reacts with DR alpha-chains, Tal 3C3 predominantly defines DP alpha-chain subunits and a high molecular weight (200-250 kD) actin binding protein known as filamin. In view of several recent reports that the cellular distribution of class II antigens may be more widespread than hitherto thought and may be expressed by cells not normally involved in specific immune functions, these findings emphasize that unexpected monoclonal antibody reactions must be interpreted with caution. It is clearly important to include both immunohistological tissue section and biochemical studies in the initial screening procedures for monoclonal antibodies in order to distinguish between specific target antigen activity and cross-reactions with unrelated molecules.

Antibodies, Monoclonal↗
PubMed1987

Molecular variation of human major histocompatibility complex DQw3 beta-chains.

Histocompatibility leukocyte antigen DQ molecules exhibit polymorphism of both DQ alpha- and beta-chains. Histocompatibility leukocyte antigen-DQw3 is associated with both DR4 and DR5 and can be further subdivided by reactivity with the monoclonal antibody TA10. To determine the molecular nature of the DQ polymorphic alleles associated with the DR4 haplotype, we have sequenced and analyzed DQ alpha and beta cDNA clones obtained from a DR4, Dw4, DQw3 cell line which is TA10-positive. The DQ alpha-chain sequence was identical to previously published sequences from the DR4 haplotype, but the DQ beta sequence differed from published DR4-DQ beta sequences obtained from DQw3-positive TA10-negative cell lines by eight amino acids, six of which were located in the beta 1 domain. Thus, the TA10 serologic determinants reside on the DQ beta-chain. A TA10-specific oligonucleotide probe was constructed based on the DQ beta sequence, and its specificity was confirmed in a panel of TA10-positive and TA10-negative cell lines. An additional band was observed in Southern blotting experiments which may indicate a donor sequence for gene conversion.

Alleles↗
PubMed1987

Identification of HLA-DP polymorphism with DP alpha and DP beta probes and monoclonal antibodies: correlation with primed lymphocyte typing.

Thirty-four lymphoblastoid cell lines that had been previously typed for HLA-DP antigens by primed lymphocyte typing (PLT) were tested by Southern blotting and by ELISA. Using two DP beta probes and a DP alpha probe with a series of enzymes, it is possible to identify restriction fragment length polymorphism (RFLP) patterns characteristic of DPw1, -2, -3, -4, and possibly -5. ELISA typing results, based on two polymorphic DP antibodies DP11.1 and ILR1, were compared with PLT-defined and RFLP-defined types. Thus, using a range of probes and enzymes it is possible to identify DP polymorphism. The value of monoclonal antibodies for such studies is demonstrated, and the molecular data can, in some cases, pinpoint the amino acids responsible for the specificity of the monoclonal antibodies.

Alleles↗
PubMed1986

Gene clusters and the evolution of the major histocompatibility system.

Gene clusters containing one or more sets of duplicated genes with related functions are probably the basic genetic functional units. The major histocompatibility systems, such as HLA and H2, are among the most complex gene clusters so far known and studied, and illustrate many of the features of their structure and evolution. They cover about one thousandth of the mammalian genome and include two major sets of cell surface products with different but related functions in the control of immune interactions, as well as genes for complement components and 21-hydroxylase. Molecular analysis has revealed an extraordinary complexity at the genetic level, reflecting a very long and involved evolutionary history. A description of the organization of the HLA system, especially the HLA-D region, and its function and polymorphism forms the basis for considering the evolution of such complex gene clusters.

Amino Acid Sequence↗
PubMed1986

DNA polymorphism of the class II genes in DR4 cells.

The restriction fragment length polymorphisms of the DR-beta, DQ-alpha and -beta genes in 11 DR4 homozygous cells of different Dw type were investigated. The results showed that, with the enzyme-probe combination studied, the DR beta restriction polymorphism patterns were constant between the different cell lines. With the DQ alpha and DQ beta probes, variations in restriction patterns were obtained. No absolute correlation was seen between RFLP and Dw types. These differences may be useful in the investigation of the association between RA and specific subsets of DR4.

Cell Line↗
PubMed1985

Structure, sequence and polymorphism in the HLA-D region.

Molecular analysis of the HLA-D region has uncovered a complex array of related genes encompassing a minimum of 6 alpha and 7 beta chain sequences. A high level of polymorphism is characteristic of the DQ alpha and beta genes, as well as DR beta. The DP genes, both alpha and beta, are also polymorphic, though to a lesser extent. The genes fit into the previously established loci: DP, DQ and DR, except for a newly-discovered sequence, DZ alpha, which is approximately equally related to all of the other alpha chain genes. Analysis of the polymorphism and evolution of the HLA-D region, by examination of the sequences, calls for several independent duplication events in the generation of this family of genes.

Base Sequence↗
PubMed1976

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↗
PubMed1976

Permanent lymphoid lines from genetically marked lymphocytes: success with lymphocytes recovered from frozen storage.

Permanent human lymphoid cell lines were established successfully from peripheral blood lymphocytes which had been separated for HL-A typing and stored in liquid nitrogen for two years. Frozen lymphocytes were chosen from two siblings who were homozygous at the LA and FOUR HL-A loci. Thawed lymphocytes were transformed with EB virus produced by the marmoset lymphoid line B95-8. No chromosome abnormalities were seen on karyotypes prepared on cells from the established human lymphoid lines using G and Q banding techniques. HL-A typing showed the expected HL-A antigens plus a considerable number of additional reactions. Separation of lymphocytes and freezing them for possible future use requires a relatively small investment. This method of preserving cells can be applied to patients with interesting genetic disorders or other biochemical markers to provide cells which can be transformed and propagated years later.

Blood Preservation↗
PubMedDate not supplied

Localization of the gene for familial adenomatous polyposis on chromosome 5.

Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although it is usually not familial, there is a rare dominantly inherited susceptibility to colon cancer, familial adenomatous polyposis (FAP; also often previously called familial polyposis coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These are sufficiently likely to give rise to adenocarcinomas to make prophylactic removal of the colon usual in diagnosed FAP individuals. Adenomas may occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. Adenomata have been suggested to be precancerous states for most colorectal tumours. Knudson has suggested that the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumour cells, and that the same gene may be involved in both familial and non-familial cases of a given tumour. Following up a case report of an interstitial deletion of chromosome 5 in a mentally retarded individual with multiple developmental abnormalities and FAP, we have now shown that the FAP gene is on chromosome 5, most probably near bands 5q21-q22.

Adenocarcinoma↗