Massachusetts Institute of Technology

Whitehead Institute for Biomedical Research

Leland Stanford Junior University

Herman N Eisen

David M Kranz

Susumu Tonegawa

Haruo Saito

Robert Samuel Langer

Margaret Alison Wheatley

Richard A Young

Jianzhu Chen

Bryan K Cho

Qian Huang

Joan F L Richmond

Deborah Palliser

Mark S Pasternack

Deborah Pallister

A Raymond Frackelton, Jr

Alonzo H Ross

The present invention relates to a method of inducing a CD8CTL response to a molecule in an individual deficient in CD4T cells comprising administering to the individual an hsp or a portion of an ATP binding domain of an hsp joined to the molecule. In one embodiment, the present invention relates to a method of treating HIV in an individual deficient in CD4T cells comprising administering to the individual an hsp or a portion of an ATP binding domain of an hsp joined to the molecule. Also encompassed by the present invention is a method of inducing a CD4independent CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule. The present invention also relates to a method of inducing a CD8CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule. In addition, the present invention relates to a composition characterized by a portion of an ATP biding domain of an hsp joined to a molecule.

Vivo CTL elicitation by heat shock protein fusion proteins maps to a discrete domain and is CD4+ T cell-independent

In vivo CTL elicitation by heat shock protein fusion proteins maps to a discrete domain and is CD4+ T cell-independent

Disclosed is a heterodimeric T lymphocyte receptor subunit. The subunit consists of variable, joining, constant, transmembrane, and cytoplasmic regions. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor subunit were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. T cell receptor subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

Heterodimeric T lymphocyte receptor subunit

Disclosed is a heterodimeric T lymphocyte receptor subunit. The subunit consists of a signal peptide, variable, joining, constant, transmembrane, and cytoplasmic regions. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor subunit were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. T cell receptor subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

Heterodimeric T lymphocyte receptor

Disclosed is a heterodimeric T lymphocyte receptor subunit. The subunit consists of variable, joining, constant, transmembrane, and cytoplasmic regions. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor submit were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. T cell receptor subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

Disclosed is a heterodimeric T lymphocyte receptor comprising an alpha and a beta subunit. Each subunit consists of a signal peptide, variable, joining, constant, transmembrane, and cytoplasmic regions. The two subunits are connected by a disulfide bond between cysteine residues located between the constant and transmembrane region. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor were determined using cDNA cones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed

Meterodimeric T lymphocyte receptor antibody

Disclosed is a heterodimeric T lymphocyte receptor comprising an alpha and a beta subunit. Each subunit consists of a signal peptide, variable, joining, constant, transmembrane, and cytoplasmic regions. The two subunits are connected by a disulfide bond between cysteine residues located between the constant and transmembrane region. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor were determined using CDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. Both the T cell receptor protein and its subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

A controlled release system for delivery of a biologically-active substance. In one embodiment, there is a delayed release of a biologically-active substance. In a second embodiment, the delayed release is preceded by an initial release of biologically active substance. In other variations of the system, there are mulitple discrete releases over time or a continuous slow release combined with discrete releases. The delayed exposure is achieved through the design and construction of the system, specifically, formation of ionically-coated microcapsules around the biologically-active substance in conjunction with a microcapsule core-degrading enzyme. Release of active substance takes place in a burst at such a time as the core degrading enzyme has reduced the core to a molecular weight too low to support enough interaction with the cationic skin to maintain its integrity as a skin. In one example, microcapsules are formed of an ionically cross-linked polysaccharide, calcium alginate, which is further ionically coated with a poly-cationic skin of poly-L-lysine. The capsule coating serves a dual purpose: to control diffusion of the biologically-active substance and the core-degrading enzyme and as a substrate for the mechanism by which the biologically-active substance is released after a time delay.

System for controlled release of biologically active compounds

A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules or a permeable polymeric matrix. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and surrounding matrix to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the surrounding matrix; or by destabilizing the liposome to break down over a period of time; or by any combination of these features.

System for delayed and pulsed release of biologically active substances

A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material, such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and microcapsule walls to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the microcapsule; or by destabilizing the liposomes to break down over a period of time; or by any combination of these features.

Disclosed is a heterodimeric T lymphocytes receptor subunit. The subunit consists of variable, joining, constant, transmembrane, and cytoplasmic regions. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor subunit were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. T cell receptor subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

T lymphocyte receptor subunit

Disclosed is a heterodimeric T lymphocyte receptor comprising an alpha and a beta subunit. Each subunit consists of a signal peptide, variable, joining, constant, transmembrane, and cytoplasmic regions. The two subunits are connected by a disulfide bond between cysteine residues located between the constant and transmembrane region. The structure, amino acid, and nucleotide sequence of the lymphocyte receptor were determined using cDNA clones derived from a functional murine cytotoxic T lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and have significant sequence homologies to immunoglobulin V and C genes. Both the T cell receptor protein and its subunits may be produced from the cDNA clones. The protein molecules may be further used for the production of T-cell clone specific antibodies.

A novel serine esterase produced by cytotoxic T lymphocytes is insolated and characterized. The protein appears to be membrane bound and has a reduced apparent molecular weight of about 28,000 daltons. Inhibition of the esterase correlates with inhibition of the cells' cytolytic activity. The serine esterase is useful in making antibody and as a target for the inhibition of cytolytic activity by T-lymphocytes, both in vivo and in vitro.

Cytotoxic t lymphocyte serine esterase and method for stimulation and

A hybridoma cell line is disclosed that secretes monoclonal antibodies which serve as a high titer, reproducible, biological reagent useful in biological/medical research for isolating and identifying phosphotyrosine-containing proteins. In addition, the antibodies have potential uses in diagnosis of a variety of diseases, including certain cancers. The antibodies, which have demonstrated affinity for a variety of molecules containing o-phosphotyrosine residues, were prepared using a synthetic analog, p-azobenzyl phosphonate (ABP) covalently linked to a carrier protein, as the antigen.

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Waban, MA, United States of America

Herman N Eisen