Soluble mhc complexes and methods of use thereof

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/12 (2006.01) A61K 38/00 (2006.01) C07K 14/74 (2006.01) C07K 19/00 (2006.01) C12N 15/09 (2006.01) C12N 15/62 (2006.01)

Patent

CA 2307178

The present invention relates to novel complexes of major histocompatibility complexe (MHC) molecules and uses of such complexes. In one aspect, the invention relates to single chain MHC class II complexes that include a class II .beta.2 chain modification, e.g., deletion of essentially the entire class II .beta.2 chain. In another aspect, the invention features single chain MHC class II which comprise an immunoglobin constant chain or fragment. Further provided are polyspecific MHC complexes comprising at least one single chain MHC class II molecule. MHC complexes of the invention are useful for a variety of applications including: 1) in vitro screens for identification and isolation of peptides that modulate activity of selected T cells, including peptides that are T cell receptor antagonists and partial agonists, and 2) methods for suppressing or inducing an immune response in a mammal.

Nouveaux complexes de molécules du complexe d'histocompatibilité majeure (MHC) et utilisations desdits complexes. Selon un aspect, la présente invention concerne des complexes de classe II du MHC à chaîne unique qui comportent une modification de la chaîne .beta.2 de classe II, par ex. une suppression de pratiquement toute la chaîne .beta.2 de classe II. Selon un autre aspect, la présente invention concerne une classe II du MHC à chaîne unique qui comporte une chaîne constante d'immunoglobuline ou un fragment de ladite chaîne. Elle concerne encore des complexes MHC polyspécifiques comportant au moins une molécule de classe II du MHC à chaîne unique. Les complexes MHC selon la présente invention sont utiles pour toute une série d'applications dont (i) les criblage in vitro en vue de l'identification et de l'isolation de peptides qui modulent l'activité de lymphocytes T sélectionnés, y compris de peptides qui sont des antagonistes de récepteurs de lymphocytes T et des agonistes partiels et (2) des procédés de suppression de la réponse immunitaire chez un mammifère.

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