Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1995-07-12
2001-05-29
Chan, Christina Y. (Department: 1644)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S282100, C530S351000
Reexamination Certificate
active
06238676
ABSTRACT:
FIELD OF THE INVENTION
The invention disclosed herein is directed to CD-1 presented antigens, compositions, cells, blocking agents and methods relating to the use of hydrophobic antigen presentation by CD1 molecules, including detection, isolation, vaccine production and administration, blocking of CD1 presentation, blocking agents, induction of CD1 expression and isolated T-cells. CD1-presented antigens of the invention stimulate T-cells to undergo an immune response.
DESCRIPTION OF THE BACKGROUND ART
The Immune System and T-cells
Animals have a complex array of molecular and cellular defenses, collectively referred to as the immune system, that recognize and attack potentially harmful foreign or endogenous but abnormal cells (respectively represented by, e.g., pathogens such as bacteria or viruses, and cancerous or pathogen-infected cells), but tolerate endogenous normal cells. When stimulated by foreign or abnormal biomolecules, the immune system undergoes a series of activities designed to neutralize and destroy the pathogens, or cancerous or pathogen-infected cells, with which the foreign or abnormal biomolecules are associated. These activities, collectively known as an immune response, may consist of a cell-mediated immune response, a humoral (antibody-mediated) immune response, or an immune response that includes elements of cell-mediated and humoral responses.
Humoral immune responses are mediated by antibodies that bind specific foreign or abnormal biomolecules. Antibodies are immunoglobulin (Ig) molecules produced by B-cells, as lymphocytes which originate in avian bursa or in mammalian bone marrow, but migrate to and mature in other organs, particularly the spleen. Robertson, M.,
Nature
301:114 (1983). Cell-mediated immune responses are the result of activities of T-cells, lymphocytes that undergo maturation within the thymus of an animal. Tizard, I. R.,
Immunology: An Introduction,
2d Ed., Saunders, Philadelphia (hereafter “Tizard”), p. 163, 1988. Both T and B-cells migrate between various organs and/or tissues within an animal's body. Lydyard, P., and Grossi, C., Chapter 3 in
Immunology,
2d Ed., Roitt, I., et al., eds., Gower Medical Publishing, London, New York, 1989.
T-cells mediate at least two general types of immunologic functions, effector and regulatory, reflecting the fact that T-cell activities vary considerably among different subpopulations of T-cells within an animal. Rook, G., Chapter
9
in
Immunology,
2d Ed., Roitt, I., et al., eds., Gower Medical Publishing, London, New York, 1989. Effector functions include delayed hypersensitivity, allograft rejection, tumor immunity, and graft-versus-host reactivity. Effector functions reflect the ability of some T-cells to secrete proteins called lymphokines, and the ability of other T-cells (“cytotoxic” or “killer” T-cells) to kill other cells. The regulatory functions of T-cells are represented by the ability of “helper” T-cells. Helper T-cells interact with, and produce biomolecules that influence the behavior of, both B-cells and cytotoxic T-cells, in order to promote and direct antibody production and cytotoxic activities, respectively. Mosier, D. E.,
Science
158:1573-1575 (1967). Other classes of T-cells, including suppressor T-cells and memory T-cells, also exist. Miedema, F., and Melief, C. J. M.,
Immunol. Today
6:258-259 (1983); Tizard, pp. 225-228.
Antigen Recognition
In order to function properly, the T- and B-cells of an animal's immune system must accurately and reliably identify the enormous number of molecular compositions derived from foreign (“non-self”), or endogenous (“self”) but abnormally expressed, compositions that are encountered. Recognition and identification by the immune system occurs at the molecular level. An antigen, a molecular composition having the potential to generate an immune response, is composed of one or more molecular-sized identifying features known as epitopes. A polypeptide antigen which has an amino acid sequence which comprises, e.g., a hundred amino acids might comprise dozens of epitopes, wherein each epitope is defined by a portion of the polypeptide comprising from about 3 to about 25 amino acids. The number of eptitopes derivable from polypeptides alone is estimated to be about ten million. Tizard, p. 25.
An antigen encountered by a T or B-cell of an animal must be identified as either being associated with normal endogenous (i.e., self) antigens, an immune response to which would be injurious to the animal, or with foreign or abnormal (i.e., non-self) antigens, to which an immune response should be mounted. As part of the immune system's means of identifying antigens, individual T and B-cells produce antigen receptors which are displayed on the T or B-cell's surface and which bind specific antigens. Turner, M., Chapter 5 in
Immunology,
2d Ed., Roitt, I., et al., eds., Gower Medical Publishing, London, New York, 1989. B-cells produce and display antigen receptors that comprise Ig molecules which have unique antigen-binding portions due to unique amino acid sequences in the variable regions of each of the two antibody subunits, known as the Ig heavy and Ig light chains. Each B-cell membrane comprises from 20,000 to 200,000 identical Ig molecules. Tizard, pp. 78-80 and 202.
The T-cell antigen receptors (TCRs) produced by and displayed on individual T-cells comprise heavy (TCR&bgr;) and light (TCR&agr;) chains (polypeptide subunits) which are linked by a disulfide bond on the T-cell surface. Each TCR&agr; and &bgr; subunit has a carboxy-terminal constant region, the amino acid sequence of which does not vary from T-cell to T-cell, and an amino-terminal variable region, the amino acid sequence of which does vary from T-cell to T-cell. When TCR&agr; and TCR&bgr; subunits associate with each other, the variable regions of the TCR&agr; and TCR&bgr; polypeptide subunits combine to form the unique antigen-binding portion of an &agr;:&bgr; TCR. A second type of TCR heterodimer, &ggr;:&dgr;, has been described but its function, if any, is unknown. Davis, M. M., and Bjorkman, P. J.,
Nature
334:395-404 (1988). Although at least one mixed TCR heterodimer of unknown function, &bgr;:&dgr; TCR, has been described, T-cells bearing &agr;:&bgr; TCR molecules are numerically dominant in mature animals. Hochstenbach, F., and Brenner, M. B.,
Nature
340:562-565 (1989).
Although each individual T- or B-cell displays identical antigen receptors, the receptor displayed varies from cell to cell; an animal's collection of different antigen receptors is thus quite diverse. The genetic basis of this diversity is as follows. The variable region of an Ig heavy chain, or that of a TCR&bgr; chain, is encoded by three gene segments, the variable (V), diversity (D) and joining (J) segments. The variable region of an Ig light chain, or that of a TCR&agr; chain, is encoded by V and J gene segments. Multiple DNA sequences encoding many different V, D and J gene segments are present as unexpressed copies in germline DNA; an analogous but different collection of variable gene segments for TCR subunits is also present. During development of an animal, genes encoding diverse variable regions are generated in individual cells of the immune system by the random joining of V, D and J, or V and J, gene segments. The process of DNA rearrangements that generates a randomly assembled variable region of an Ig heavy or TCR&bgr; subunit is called V-D-J joining; the analogous process that generates a rearranged variable region of an Ig light or TCR&agr; subunit is called V-J joining. Sakano, H., et al.,
Nature
280:288-294 (1979); Early, P., et al., Cell 19:981-992 (1980); Alt, F. W., et al.,
Science
238:1079-1087 (1987); Harlow, E., and Lane, D.,
Antibodies: A Laboratory Manual,
Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pages 10-18, 1988; Davis, M. M., and Bjorkman, P. J.,
Nature
334:395-404 (1988).
A functionally rearranged Ig or TCR subunit gene is one in which the DNA rearrangements of V-D-J or V-J joining have not resulted in a reading frame t
Beckman Evan M.
Brenner Michael B.
Furlong Stephen T.
Porcelli Steven A.
Brigham and Women's Hospital
Chan Christina Y.
DiBrino Marianne
Wolf Greenfield & Sacks PC
LandOfFree
Presentation of hydrophobic antigens to T-cells by CD1... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Presentation of hydrophobic antigens to T-cells by CD1..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Presentation of hydrophobic antigens to T-cells by CD1... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2520121