PMID- 33649568
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20221123
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Linking)
VI  - 39
IP  - 8
DP  - 2021 Aug
TI  - Affinity-matured HLA class II dimers for robust staining of antigen-specific 
      CD4(+) T cells.
PG  - 958-967
LID - 10.1038/s41587-021-00836-4 [doi]
AB  - Peptide-major histocompatibility complex (pMHC) multimers enable the detection of 
      antigen-specific T cells in studies ranging from vaccine efficacy to cancer 
      immunotherapy. However, this technology is unreliable when applied to pMHC class 
      II for the detection of CD4(+) T cells. Here, using a combination of molecular 
      biological and immunological techniques, we cloned sequences encoding human 
      leukocyte antigen (HLA)-DP, HLA-DQ and HLA-DR molecules with enhanced CD4 binding 
      affinity (with a K(d) of 8.9 +/- 1.1 microM between CD4 and affinity-matured HLA-DP4) 
      and produced affinity-matured class II dimers that stain antigen-specific T cells 
      better than conventional multimers in both in vitro and ex vivo analyses. Using a 
      comprehensive library of dimers for HLA-DP4, which is the most frequent HLA 
      allele in many ancestry groups, we mapped 103 HLA-DP4-restricted epitopes derived 
      from diverse tumor-associated antigens and cloned the cognate T-cell antigen 
      receptor (TCR) genes from in vitro-stimulated CD4(+) T cells. The availability of 
      affinity-matured class II dimers across HLA-DP, HLA-DQ and HLA-DR alleles will 
      aid in the investigation of human CD4(+) T-cell responses.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Sugata, Kenji
AU  - Sugata K
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Matsunaga, Yukiko
AU  - Matsunaga Y
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Yamashita, Yuki
AU  - Yamashita Y
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Nakatsugawa, Munehide
AU  - Nakatsugawa M
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Guo, Tingxi
AU  - Guo T
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Halabelian, Levon
AU  - Halabelian L
AUID- ORCID: 0000-0003-4361-3619
AD  - Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
FAU - Ohashi, Yota
AU  - Ohashi Y
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Saso, Kayoko
AU  - Saso K
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Rahman, Muhammed A
AU  - Rahman MA
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Anczurowski, Mark
AU  - Anczurowski M
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Wang, Chung-Hsi
AU  - Wang CH
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Murata, Kenji
AU  - Murata K
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Saijo, Hiroshi
AU  - Saijo H
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Kagoya, Yuki
AU  - Kagoya Y
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Ly, Dalam
AU  - Ly D
AUID- ORCID: 0000-0002-1177-0225
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Burt, Brian D
AU  - Burt BD
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
FAU - Butler, Marcus O
AU  - Butler MO
AUID- ORCID: 0000-0002-9840-7057
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
AD  - Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
FAU - Mak, Tak W
AU  - Mak TW
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Hirano, Naoto
AU  - Hirano N
AUID- ORCID: 0000-0001-9070-4754
AD  - Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer 
      Research, Princess Margaret Cancer Centre, University Health Network, Toronto, 
      Ontario, Canada. naoto.hirano@uhnresearch.ca.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada. 
      naoto.hirano@uhnresearch.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210301
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (CD4 Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - CD4 Antigens/chemistry/metabolism
MH  - CD4-Positive T-Lymphocytes/chemistry/cytology/metabolism
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - *HLA Antigens/chemistry/metabolism
MH  - *Histocompatibility Antigens Class II/chemistry/metabolism
MH  - Humans
MH  - Protein Binding
MH  - Staining and Labeling/*methods
EDAT- 2021/03/03 06:00
MHDA- 2021/09/22 06:00
CRDT- 2021/03/02 06:18
PHST- 2019/07/30 00:00 [received]
PHST- 2021/01/15 00:00 [accepted]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2021/03/02 06:18 [entrez]
AID - 10.1038/s41587-021-00836-4 [pii]
AID - 10.1038/s41587-021-00836-4 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2021 Aug;39(8):958-967. doi: 10.1038/s41587-021-00836-4. Epub 
      2021 Mar 1.