Institut National De La Sante Et De La Recherche Medicale

Centre National De La Recherche Scientifique

Bristol-Myers Squibb Compnay

E. R. Squibb Sons, Inc.

Université Louis Pasteur

Universite Louis Pasteur, Strasbourg 1

Diane J Mathis

Christophe O Benoist

Anne-Sophie Korganow

Mariana Maccioni

Hong Ji

Isao Matsumoto

Dominic Cosgrove

Valerie Kouskoff

The present invention relates to the use of antibodies against glucose-6-phosphate isomerase (GPI) and like protein for diagnosis of arthritis and the use of said protein for treatment of arthritis. It is also aimed at a process for isolating monoclonal antibodies capable of transferring arthritis and antibodies thereof, as well as a method for determining the anti-arthritis potential of a composition.

Use of glucose-6-phosphate isomerase and antibodies thereto for the diagnosis and therapy of arthritis, and test of anti-arthritic compounds

The present invention relates to the use of antibodies against glucose-6-phosphate isomerase and like protein for diagnosis of arthritis and the use of said protein for treatment of arthritis. It is also aimed at a process for isolating monoclonal antibodies capable of transferring arthritis and antibodies thereof, as well as a method for determining the anti-arthritic potential of a composition.

Use of gluclose-6-phosphate isomerase and antibodies thereto for the diagnosis and therapy of arthritis, and test of anti-arthritic compounds

A transgenic animal model for arthritis is disclosed. The arthritic condition results from genetic (or immunologic) manipulations that result in the T cell receptor (TCR) repertoire of the animal being substantially limited relative to the TCR repertoire of a wildtype control animal. The TCR repertoire of the arthritic animal, albeit limited, is functionally viable. In a preferred embodiment, the invention relates to transgenic arthritic mice wherein arthritis results from (1) a transgenic allele which encodes and expresses TCR .alpha. and .beta. subunits that combine in T lymphocytes of the transgenic animal to form a TCR that recognizes an antigen comprising one or more epitopes of an oligopeptide derived from amino acids 41-61 of bovine pancreatic ribonuclease and/or (2) polypeptide arthritogenic self antigens derived from endogenous proteins. The transgenic arthritic mice of the invention provides an animal model which faithfully mimics rheumatoid arthritis and by which human arthritogenic and therapeutic anti-arthritic compositions are evaluated. Also provided herein are therapeutic oligopeptides derived from the variable regions of the TCRs of the transgenes of the invention and/or from the amino acid sequence of proteins comprising endogenous polypeptide arthritogenic antigens.

Transgenic arthritic mice expressing a T-cell receptor transgene

The present invention provides mice which are deficient in the normal expression of one or more MHC class II genes, to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous, homozygous or chimeric for such deficiency, as well as to the use of any of the above, especially in situations where the absence of at least one MHC gene, or the normal expression thereof, is desirable.

Genetically engineered mice containing alterations in the MHC class II

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Strasbourg, France

Diane J Mathis