公开(公告)号：US20220291215A1

公开(公告)日：2022-09-15

申请号：US17631818

申请日：2020-07-29

Applicant: University Health Network

Inventor： Naoto HIRANO ,  Munehide NAKATSUGAWA ,  Yuki YAMASHITA ,  Kenji SUGATA ,  Muhammed Aashiq RAHMAN

IPC: G01N33/569 ,  G01N33/554

Abstract: The present disclosure is directed to methods of identifying MHC class II-specific T cell receptors (TCRs). In certain aspects, the method comprises contacting a T cell with a complex comprising an (i) MHC class II molecule having a higher affinity for CD4 than naturally occurring MHC class II molecules and (ii) a peptide, e.g., an epitope. In certain aspects, the HLA class II molecule comprises a beta chain having one or more mutations relative to a wild-type beta chain sequence.

公开(公告)号：US20230192809A1

公开(公告)日：2023-06-22

申请号：US17814401

申请日：2022-07-22

Applicant: University Health Network

Inventor： Naoto HIRANO ,  Munehide NAKATSUGAWA ,  Muhammed Aashiq RAHMAN ,  Kenji MURATA

IPC: C07K14/74 ,  C07K7/06

CPC classification number: C07K14/70539 ,  C07K7/06 ,  C07K2319/02 ,  C07K2319/21

Abstract: There is provided herein, the use of mammalian derived HLA class I molecule for in vitro peptide exchange. For example, there is provided a method of producing an HLA class I molecule complexed to a pre-selected peptide comprising: (a) providing a mammalian derived HLA class I molecule complexed to an existing peptide; (b) incubating, in vitro, the HLA class I molecule complexed to the existing peptide with the pre-selected peptide, wherein the pre-selected peptide is at a concentration sufficient to replace the existing peptide to produce the HLA class I molecule complexed to the pre-selected peptide; and the HLA class I molecule comprises α1, α2, α3 and β2m domains.

公开(公告)号：US20220281948A1

公开(公告)日：2022-09-08

申请号：US17631820

申请日：2020-07-29

Applicant: University Health Network

Inventor： Naoto HIRANO ,  Munehide NAKATSUGAWA ,  Yuki YAMASHITA ,  Muhammed Aashiq RAHMAN ,  Tingxi GUO

IPC: C07K14/74 ,  C12N5/0783 ,  A61P35/00

Abstract: The present disclosure is directed to HLA class II molecules having a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecule comprises a DP beta chain having (i) an amino acid other than leucine at a position corresponding to amino acid residue 112 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 141 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure are directed to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecule, cells comprising the same, and methods of use thereof.