Walter F. Bodmer

Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis

Antibody-secreting hybrid cells have been derived from a fusion between mouse myeloma cells and spleen cells from a mouse immunized with membrane from human tonsil lymphocyte preparations. Hybrids secreting antibodies to cell surface antigens were detected by assaying culture supernatants for antibody binding to human tonsil cells. Six different antibodies (called W6/1, /28, /32, /34, /45 and /46 were analyzed. These were either against antigens of wide tissue distribution (W6/32, /34, and /46) or mainly on erythrocytes (W6/1 and W6/28). One of the anti-erythrocyte antibodies (W6/1) detected a polymorphic antigen, since blood group A1 and A2 erythrocytes were labeled while B and O were not. Antibodies W6/34, /45 and /46 were all against antigens which were mapped to the short arm of chromosome 11 by segregation analysis of mouse-human hybrids. Immunoprecipitation studies suggest that W6/45 antigen may be a protein of 16,000 dalton, apparent molecular weight, while W6/34 and /46 antigens could not be detected by this technique. Antibody W6/32 is against a determinant common to most, if not all, of the 43,000 dalton molecular weight chains of HLA-A, B and C antigens. This was established by somatic cell genetic techniques and by immunoprecipitation analysis. Tonsil leucocytes bound 370,000 W6/32 antibody molecules per cell at saturation. The hybrid myelomas W6/32 and W6/34 have been cloned, and both secrete an IgG2 antibody. W6/32 cells were grown in mice, and the serum of the tumor-bearing animals contained greater than 10 mg/ml of monoclonal antibody. The experiments established the usefulness of the bybrid myeloma technique in preparing monospecific antibodies against human cell surface antigens. In particular, this study highlights the possibilities not only of obtaining reagents for somatic cell genetics, but also of obtaining mouse antibodies detecting human antigenic polymorphisms.

Nomenclature for factors of the HLA system, 2010

The WHO Nomenclature Committee for Factors of the HLA System met following the 14th International HLA and Immunogenetics Workshop in Melbourne, Australia in December 2005 and Buzios, Brazil during the 15th International HLA and Immunogenetics Workshop in September 2008. This report documents the additions and revisions to the nomenclature of HLA specificities following the principles established in previous reports (1–18).

A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz–Jeghers syndrome, (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p (ref. 3). We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1 (ref. 4), has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1 (ref. 5), and weaker similarity to many other protein kinases. Peutz–Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.

Common and rare variants in multifactorial susceptibility to common diseases

Here, we give a historical overview of the search for genetic variants that influence the susceptibility of an individual to a chronic disease, from RA Fishers seminal work to the current excitement of whole-genome association studies (WGAS). We then discuss the concepts behind the identification of common variants as disease causal factors and contrast them to the basic ideas that underlie the rare variant hypothesis. The identification of rare variants involves the careful selection of candidate genes to examine, the availability of highly efficient resequencing techniques and the appropriate assessment of the functional consequences of the implicated variant. We believe that this strategy can be successfully applied at present in order to unravel the contribution of rare variants to the multifactorial inheritance of common diseases, which could lead to the implementation of much needed preventative screening schemes.

Monoclonal Antibodies for Analysis of the HLA System

III Antibodies A Monoclonal antibodies against determinants of the HLA-A,-B,-C glycoproteins and pjmicroglobulin 1. Antibodies against species specific, non-polymorphic determinants 2. Antibodies against polymorphic HLA-A,-B,-C determinants B Monoclonal antibodies against HLA-DRw determinants 1. Antibody against a species specific HLA-DRw determinants 2. Antibodies against polymorphic HLA-DRw determinants

Monoclonal antibody to cytokeratin for use in routine histopathology.

CAM 5.2 is a murine monoclonal antibody, raised against the colon carcinoma cell line HT29, which recognises lower molecular weight intracellular cytokeratin proteins within secretory epithelia. Extensive indirect immunohistochemical studies have confirmed that this antibody stains formalin fixed (and freshly frozen) normal and malignant human tissue in a consistent manner. Reliable staining of conventionally processed pathological tissues provides more accurate identification and staging of human malignant epithelial diseases.

The Eurasian Heartland: A continental perspective on Y-chromosome diversity

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.

TARGETING OF IODINE-123-LABELLED TUMOUR-ASSOCIATED MONOCLONAL ANTIBODIES TO OVARIAN, BREAST, AND GASTROINTESTINAL TUMOURS

Two tumour-associated monoclonal antibodies, HMFG1 and HMFG2, were labelled with iodine-123 and used to detect primary and metastatic ovarian, breast, and gastrointestinal neoplasms by external body scintigraphy in twenty patients with advanced disease. Tumours became visible 3 min to 18 h after injection of labelled antibody. The presence of antibody in the tumours was confirmed by autoradiography and immunoperoxidase staining of surgically removed tissues. The mean tumour uptake of radiolabel was 0.6% of the injected amount. These antibodies can therefore localise specifically to tumours and successful imaging can thus be achieved. This method can complement existing diagnostic techniques and also provide a basis for a selective therapeutic approach to malignant disease.

Nomenclature for factors of the HLA system, 1991

Abstract The WHO Nomenclature Committee for factors of the HLA system met in Hakone after the Eleventh International Histocompatibility Workshop and Conference during November 1991 to consider additions and revisions to the nomenclature of specificities defined by both molecular and serological techniques following the principles established in previous reports (1 – 10).

Nomenclature for Factors of the HLA System, 1996

Recently a number of new genes have been identified within the HLA region including some whose functions are related to HLA class I and I1 genes. The Committee discussed what its strategy should be for the naming of these and further new Julia G. Bodmer, Steven 6. E. Marsh, Ekkehard D. Albert, Walter F. Bodmer, Ronald E. lontrop, Dominique Charron, Bo Dupant, Henry A. Erlich, Renee Fauchet, Bernard Mach, Wolfgang R. Mayr, Peter Parham, Takehlko Sasazuki, Geziena M. Th. Schreuder, Jack 1. Strominger, Arne Svejgaard and Paul la Terasaki