Abstract: An improved method for producing human antibodies in SCID mice is provided. The improvement includes the use of dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents.

Abstract: A transgenic animal with alterations in an H2-O gene is prepared by introduction of an altered H2-O gene into a host animal. The resulting transgenic animals produce a substantially greater frequency of high affinity antibodies compared to H2-O wild type animals. A method for the production of high affinity antibodies is disclosed.

Abstract: The present invention provides a method of biasing the immune response of a mammal toward a desired epitope of a chosen antigen, particularly a functionally-relevant epitope. In preferred embodiments, the epitope-biasing method leads to fully-human antibodies of defined specificity with affinities of 10 nM to 50 pM. The invention further provides antibody libraries biased to tissues and to cell types, for use in generating epitope expression profiles useful for characterizing unknown genes. When all aspects of the present invention are combined, they result in an integrated system for defining critical epitopes on newly discovered gene products and rapidly devloping therapeutic grade antibodies to those critical epitopes.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: The subject invention relates to methods of producing non-human transgenic mammals which produce various oligosaccharides and glycoconjugates in their milk. Additionally, the subject invention relates to the mammals themselves, the milk which they produce, compositions comprising the milk, fractions of the milk, and the purified oligosaccharides, as well as glyconjugates, present in the milk.

Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: DNA constructs are provided of epitope-tagged proteins or protein fragments which are conveniently purified with immunoaffinity chromatography such as epitope-tagged prion proteins (PrP). Transgenic animals expressing an epitope-tagged protein are provided, including transgenic animals expressing epitope-tagged PrP. Methods for distinguishing between the conformational shapes of a protein and a convenient method for isolating a tagged protein by immunoaffinity chromatographic methods are provided.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: Transgenic mice which constitutively express an antibody-type molecule encoded by the transgene and which has an IgE heavy chain constant region and is specific for a pre-defined antigen, provide an allergic reaction to that antigen without prior sensitization and are useful as allergy models.

Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: The invention relates to a method for making monoclonal antibodies having pre-defined specificity for an epitope characteristic of or unique to a single form of a polymorphic protein. The method includes constructing a first transgenic animal to express a first form of a polymorphic protein encoded by a first allele of a gene encoding the protein; constructing a second transgenic animal to express a second form of the polymorphic protein encoded by a second allele of the gene encoding the protein; and immunizing the first transgenic animal with cells from the second transgenic animal expressing the second form of the polymorphic protein to induce an immune response in the first transgenic animal yielding an antibody specific for an epitope peculiar to the second form of the polymorphic protein. The invention further includes hybridoma cells secreting a monoclonal antibody specific for the second form of the protein.