Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1995-07-14
1999-04-06
Feisee, Lila
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4242031, 4242341, 514 2, 514 8, 514 12, 514 23, 514 54, 530300, 530324, A61K 3900, A61K 3800, A01N 3718, A01N 4304
Patent
active
058914382
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of Invention
The field of this invention relates to antigenic stimulation of specific immune responses. Specifically, the invention relates to identification of B cell superantigens and their use as adjuvants and/or carrier proteins to enhance a specific immune response to bacterial or viral pathogens having polysaccharide or glycoprotein components in their cell walls, cell membranes, capsules or envelopes. More particularly, it relates to a method of enhancing the immune response by administration of said polysaccharide or glycoprotein with a B cell superantigen either concomitantly or in a chemically conjugated form.
2. History of the Prior Art
For a complete understanding of the invention, a brief summary of the role of clonal development of B cells in immune responses is helpful.
In the germ-line cells, there are three sets of germ-line genes involved in immunoglobulin coding: one set codes for the heavy chains, and the other two code for two types of light chain designated by the Greek letters kappa (.kappa.) and lambda (.lambda.), which differ significantly in the amino acid sequence of their constant domains. Immunoglobulins are composed of heavy and light chain heterodimers, which contribute to the conventional antigen binding site in the Fab portion. B cells themselves are lymphocytes which have immunoglobins on their cell surface which serve as receptors for antigens. Binding of antigen, in most instances together with additional signals from T cells, causes the original B cell to proliferate, forming clones. The expanded clonal population differentiates into memory cells and plasma cells, the latter of which synthesize and secrete antibodies which generally will have identical binding sites for the antigen which triggered the B cell activation. Polyclonal activation occurs when certain antigens (known to include mitogens and the Epstein-Barr virus) stimulate clonal expansion regardless of the antigen specificity of the B cells involved.
The human antibody repertoire is responsible for the acquisition of a dynamic and responsive immune defense system, but dysregulation within the B cell compartment can result in a wide spectrum of clinical conditions, including inappropriate B cell clonal expansions (e.g., B cell neoplasms), inadequate immune defense from infection, or autoimmune disease. During fetal development, antibody specificities are acquired slowly in a developmentally ordered fashion.
Referring for purposes of illustration to humans, the V, J, and D genes code in human cells for the variable regions of the antibody molecule and the C genes code for the constant regions. Each of the three germ-line sets contain from two to at least 300 alternative V genes, together with a small number of alternative J genes; the heavy-chain set also has alternative D genes. Any of these genes can contribute in the variable regions of antibody molecules. Each set has from one to five alternative C genes coding for different constant regions.
As a germ-line cell differentiates into a mature but "naive" B cell (i.e. one that is reactive to but has not yet encountered its matching antigen), somatic recombination of the germ-line genes takes place. In each cell, one of the V genes from each of the three germ-line sets is "selected" by an unknovin molecular process, together with one of the adjacent J genes (and in heavy chains, also with one of the D genes). These selected genes are brought together in the genome when the intervening DNA is excised. The basis of diversity in the antigen-recognition structure of an antibody molecule rests initially on this recombination event, since different genes are recombined in different B cells.
Although the first source of variation in the structure of the antibody molecule is brought about by somatic recombination of alternative V, D and J genes, further diversity in the amino acid sequence of the variable domains results from variable recombinations; i.e., slight variations in the exact location of the "cutting points" as first th
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Feisee Lila
The Regents of the University of California
Ungar Susan
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