Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
1998-07-08
2001-08-21
Swartz, Rodney P. (Department: 1645)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C424S185100, C424S192100, C435S041000, C435S069100, C435S320100, C530S300000, C536S023100, C536S023500
Reexamination Certificate
active
06277959
ABSTRACT:
FIELD OF THE INVENTION
The present invention contemplates compositions related to genes found in lymphocytes, e.g., cells which function in the immune system. These genes are useful markers, and may function in controlling development, differentiation, and/or physiology of the mammalian immune system. In particular, the application provides nucleic acids, proteins, antibodies, and methods of using them.
BACKGROUND OF THE INVENTION
The circulating component of the mammalian circulatory system comprises various cell types, including red and white blood cells of the erythroid and myeloid cell lineages. See, e.g., Rapaport (1987)
Introduction to Hematology
(2d ed.) Lippincott, Philadelphia, Pa.; Jandl (1987)
Blood: Textbook of Hematology,
Little, Brown and Co., Boston, Mass.; and Paul (ed.) (1993)
Fundamental Immunology
(3d ed.) Raven Press, N.Y.
Dendritic cells (DC) are antigen-processing or presenting cells, and are found in all tissues of the body. See Steinman (1991)
Annual Review of Immunology
9:271-296; and Banchereau and Schmitt (eds. 1994)
Dendritic Cells in Fundamental and Clinical Immunology
Plenum Press, N.Y. These DC can be classified into various categories, including: interstitial dendritic cells of the heart, kidney, gut, and lung; Langerhans cells in the skin and mucous membranes; interdigitating dendritic cells in the thymic medula and secondary lymphoid tissue; and blood and lymph dendritic cells. Although dendritic cells in each these compartments are CD45+ leukocytes that apparently arise from bone marrow, they may exhibit differences that relate to maturation state and microenvironment.
These dendritic cells efficiently process and present antigens to, e.g., T cells. They stimulate responses from naive and memory T cells in the paracortical area of secondary lymphoid organs. There is some evidence for a role in induction of tolerance.
The primary and secondary B-cell follicles contain follicular dendritic cells that trap and retain intact antigen as immune complexes for long periods of time. These dendritic cells present native antigen to B cells and are likely to be involved in the the affinity maturation of antibodies, the generation of immune memory, and the maintenance of humoral immune responses.
Monocytes are phagocytic cells that belong to the mononuclear phagocyte system and reside in the circulation. See Roitt (ed)
Encyclopedia of Immunology
Academic Press, San Diego. These cells originate in the bone marrow and remain only a short time in the marrow compartment once they differentiate. They then enter the circulation and can remain there for a relatively long period of time, e.g., a few days. The monocytes can enter the tissues and body cavities by the process designated diapedesis, where they differentiate into macrophages and possibly into dendritic cells. In an inflammatory response, the number of monocytes in the circulation may double, and many of the increased number of monocytes diapedese to the site of inflammation.
Antigen presentation refers to the cellular events in which a proteinaceous antigen is taken up, processed by antigen presenting cells (APC), and then recognized to initiate an immune response. The most active antigen presenting cells have been characterized as the macrophages, which are direct developmental products from monocytes; dendritic cells; and certain B cells.
Macrophages are found in most tissues and are highly active in internalization of a wide variety of protein antigens and microorganisms. They have a highly developed endocytic activity, and secrete many products important in the initiation of an immune response. For this reason, it is believed that many genes expressed by monocytes or induced by monocyte activation are likely to be important in antigen uptake, processing, presentation, or regulation of the resulting immune response.
However, dendritic cells and monocytes are poorly characterized, both in terms of proteins they express, and many of their functions and mechanisms of action, including their activated states. In particular, the processes and mechanisms related to the initiation of an immune response, including antigen pocessing and presentation, remain unclear. The absence of knowledge about the structural, biological, and physiological properties of these cells limits their understanding. Thus, medical conditions where regulation, development, or physiology of antigen presenting cells is unusual remain unmanageable.
SUMMARY OF THE INVENTION
The present invention is based, in part, upon the discovery of various mammalian Dendritic Cell Membrane Protein (DCMP) genes, exemplified by the specific DCMP1 and DCMP2 embodiments. Distribution data indicates a broader cellular distribution, and structural data suggests some function. The DCMP1 exhibits similarity to a class of lectins and asialoglycoprotein receptors. The DCMP2 embodiments described exhibit significant sequence similarity to a macrophage cell asialoglycoprotein receptor. The invention embraces agonists and antagonists of the gene products, e.g., mutations (muteins) of the natural sequences, fusion proteins, chemical mimetics, antibodies, and other structural or functional analogs. It is also directed to isolated genes encoding proteins of the invention. Various uses of these different protein or nucleic acid composition are also provided.
In particular embodiments, the invention provides a nucleic acid encoding: at least 17 contiguous amino acids from SEQ ID NO: 2 or 8; a polypeptide selected from: GVSELQEHTT QKAHLGHCPH CPSVCVP (residues 118-144 of SEQ ID NO: 4); QVATLNNNAS TEGTCC (residues 166-181 of SEQ ID NO: 4); or WKPGQPDNWQ GHGLG (residues 263-277 of SEQ ID NO: 4); or sequence exhibiting both: at least 17 contiguous amino acids from DCMP2v (see SEQ ID NO: 4); and a lack of a segment of at least 12 contiguous amino acids from FKNGPLPLQS LLQRLRWGPC HLLLWLGLGL LLLVIIC (see SEQ ID NO: 4). Certain embodiments include the polynucleotide encoding a mature polypeptide of: SEQ ID NO: 2 or 8; DCMP21 (see SEQ ID NO: 4); DCMP2s (see SEQ ID NO: 4); or DCMP2v (see SEQ ID NO: 4). Other preferred embodiments include such a polynucleotide which hybridizes at 55° C., less than 500 mM salt, and 50% formamide to: the coding portion of SEQ ID NO: 1 or 7; or GTA TCT GAG CTC CAG GAA CAC ACT ACG CAG AAG GCA CAC CTA GGC CAC TGT CCC CAC TGC CCA TCT GTG TGT GTC CCA (see SEQ ID NO: 3). Certain preferred embodiments include those comprising: at least 35 contiguous nucleotides of SEQ ID NO: 1; or at least 35 contiguous nucleotides from GTA TCT GAG CTC CAG GAA CAC ACT ACG CAG AAG GCA CAC CTA GGC CAC TGT CCC CAC TGC CCA TCT GTG TGT GTC CCA (see SEQ ID NO: 3).
The invention further embraces expression vectors, and host cells containing them, including a eukaryotic cell. Methods are provides for making an antigenic polypeptide comprising expressing a recombinant polynucleotide.
Methods of detection are provided, e.g., comprising contacting a polynucleotide with a probe that hybridizes, under stringent conditions, to at least 25 contiguous nucleotides of: the coding portion of SEQ ID NO: 1; or GTA TCT GAG CTC CAG GAA CAC ACT ACG CAG AAG GCA CAC CTA GGC CAC TGT CCC CAC TGC CCA TCT GTG TGT GTC CCA (see SEQ ID NO: 3); to form a duplex, wherein detection of said duplex indicates the presence of said polynucleotide. Also provided are kits comprising a compartment containing a probe that hybridizes, under stringent hybridization conditions, to at least 17 contiguous nucleotides of such a polynucleotide to form a duplex. Preferably, the kit contains a probe which is detectably labeled. Further aspects of the invention provide methods using at least one strand of those nucleic acids to form a duplex nucleic acid, comprising a step of contacting such strand to a sample to a complementary strand capable of specifically hybridizing. In preferred embodiments, the method allows detection of the duplex; or allows histological localization of the duplex.
Binding compounds are provided, e.g., antibodies, comprising an antibody binding site which specifically binds to: at
Bates Elizabeth Esther Mary
Ford John
Lebecque Serge J. E.
Ravel Odile
Saeland Sem
McLaughlin Jaye
Schering Corporation
Swartz Rodney P.
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