Use of multivalent chimeric peptide-loaded, mhc/ig molecules...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/85 (2006.01) A61K 35/12 (2006.01) A61K 38/17 (2006.01) A61K 39/145 (2006.01) A61K 39/21 (2006.01) A61K 39/385 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) C07K 14/11 (2006.01) C07K 14/15 (2006.01) C07K 14/74 (2006.01) G01N 33/53 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2303396

To increase the effective affinity of soluble analogs of peptide/MHC molecules for their cognate ligands, divalent peptide/MHC complexes were constructed. Using a recombinant DNA strategy, DNA encoding the MHC class I was ligated to DNA coding for murine Ig heavy chain. MHC/Ig complexes were exploited to homogeneously load with peptides of interest. The results of flow cytometry demonstrated that the pepMHC/Ig complexes bound specifically with high affinity to cells bearing their cognate receptors. pepMHC/Ig complexes are also useful in modulating effector functions of antigen-specific T cells. These pepMHC/Ig complexes are useful for studying TCR/MHC interactions and lymphocyte tracking and have uses as specific regulators of immune responses.

On a élaboré des complexes peptide/CMH divalents pour améliorer l'affinité effective des analogues solubles de molécules du type peptide/CMH vis-à-vis de leurs ligands correspondants. En utilisant une technique à base d'ADN recombiné, on a ligaturé de l'ADN codant le CMH de classe I sur de l'ADN codant la chaîne polypeptidique lourde Ig murine. Les complexes CMH/Ig ont permis de procéder à un chargement homogène avec les peptides visés. Les résultats de la cytométrie de flux ont montré que les complexes ?pep¿CMH/Ig avaient une haute affinité de liaison spécifique avec des cellules comportant leurs récepteurs correspondants. Par ailleurs, les complexes ?pep¿CMH/Ig interviennent utilement dans la modulation des fonctions effectrices des cellules T spécifiques de l'antigène. En outre, lesdits complexes interviennent utilement dans l'étude des interactions du type récepteur des cellules T (TcR)/CMH et dans le repérage des lymphocytes, et ils répondent à différentes utilisations en tant que régulateurs spécifiques des réponses immunes.

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