HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients

HLA-B∗13:01 is associated with dapsone (DDS)-induced hypersensitivity, and it has been shown that CD4+ and CD8+ T cells are activated by DDS and its nitroso metabolite (nitroso dapsone [DDS-NO]). However, there is a need to define the importance of the HLA association in the disease pathogenesis. Th...

Full description

Saved in:
Bibliographic Details
Main Authors: Qing Zhao, Mubarak Almutairi, Arun Tailor, Adam Lister, Nicolas Harper, James Line, Xiaoli Meng, Jirawat Pratoomwun, Kanoot Jaruthamsophon, Chonlaphat Sukasem, Yonghu Sun, Lele Sun, Monday O. Ogese, David J. MacEwan, Munir Pirmohamed, Jianjun Liu, David A. Ostrov, Hong Liu, Furen Zhang, Dean J. Naisbitt
Other Authors: Ramathibodi Hospital
Format: Article
Published: 2022
Subjects:
Online Access:https://repository.li.mahidol.ac.th/handle/123456789/76019
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Mahidol University
id th-mahidol.76019
record_format dspace
spelling th-mahidol.760192022-08-04T16:11:59Z HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients Qing Zhao Mubarak Almutairi Arun Tailor Adam Lister Nicolas Harper James Line Xiaoli Meng Jirawat Pratoomwun Kanoot Jaruthamsophon Chonlaphat Sukasem Yonghu Sun Lele Sun Monday O. Ogese David J. MacEwan Munir Pirmohamed Jianjun Liu David A. Ostrov Hong Liu Furen Zhang Dean J. Naisbitt Ramathibodi Hospital A-Star, Genome Institute of Singapore University of Liverpool Faculty of Medicine Ramathibodi Hospital, Mahidol University Huachiew Chalermprakiet University University of Florida College of Medicine Shandong Provincial Hospital Biochemistry, Genetics and Molecular Biology Medicine HLA-B∗13:01 is associated with dapsone (DDS)-induced hypersensitivity, and it has been shown that CD4+ and CD8+ T cells are activated by DDS and its nitroso metabolite (nitroso dapsone [DDS-NO]). However, there is a need to define the importance of the HLA association in the disease pathogenesis. Thus, DDS- and DDS-NO‒specific CD8+ T-cell clones (TCCs) were generated from hypersensitive patients expressing HLA-B∗13:01 and were assessed for phenotype and function, HLA allele restriction, and killing of target cells. CD8+ TCCs were stimulated to proliferate and secrete effector molecules when exposed to DDS and/or DDS-NO. DDS-responsive and several DDS-NO‒responsive TCCs expressing a variety of TCR sequences displayed HLA class-I restriction, with the drug (metabolite) interacting with multiple HLA-B alleles. However, activation of certain DDS-NO‒responsive CD8+ TCCs was inhibited with HLA class-II block, with DDS-NO binding to HLA-DQB1∗05:01. These TCCs were of different origin but expressed TCRs displaying the same amino acid sequences. They were activated through a hapten pathway; displayed CD45RO, CD28, PD-1, and CTLA-4 surface molecules; secreted the same panel of effector molecules as HLA class-I‒restricted TCCs; but displayed a lower capacity to lyse target cells. To conclude, DDS and DDS-NO interact with a number of HLA molecules to activate CD8+ TCCs, with HLA class-II‒restricted CD8+ TCCs that display hybrid CD4‒CD8 features also contributing to the promiscuous immune response that develops in patients. 2022-08-04T08:05:34Z 2022-08-04T08:05:34Z 2021-10-01 Article Journal of Investigative Dermatology. Vol.141, No.10 (2021), 2412-2425.e2 10.1016/j.jid.2021.03.014 15231747 0022202X 2-s2.0-85105544537 https://repository.li.mahidol.ac.th/handle/123456789/76019 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85105544537&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
Qing Zhao
Mubarak Almutairi
Arun Tailor
Adam Lister
Nicolas Harper
James Line
Xiaoli Meng
Jirawat Pratoomwun
Kanoot Jaruthamsophon
Chonlaphat Sukasem
Yonghu Sun
Lele Sun
Monday O. Ogese
David J. MacEwan
Munir Pirmohamed
Jianjun Liu
David A. Ostrov
Hong Liu
Furen Zhang
Dean J. Naisbitt
HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
description HLA-B∗13:01 is associated with dapsone (DDS)-induced hypersensitivity, and it has been shown that CD4+ and CD8+ T cells are activated by DDS and its nitroso metabolite (nitroso dapsone [DDS-NO]). However, there is a need to define the importance of the HLA association in the disease pathogenesis. Thus, DDS- and DDS-NO‒specific CD8+ T-cell clones (TCCs) were generated from hypersensitive patients expressing HLA-B∗13:01 and were assessed for phenotype and function, HLA allele restriction, and killing of target cells. CD8+ TCCs were stimulated to proliferate and secrete effector molecules when exposed to DDS and/or DDS-NO. DDS-responsive and several DDS-NO‒responsive TCCs expressing a variety of TCR sequences displayed HLA class-I restriction, with the drug (metabolite) interacting with multiple HLA-B alleles. However, activation of certain DDS-NO‒responsive CD8+ TCCs was inhibited with HLA class-II block, with DDS-NO binding to HLA-DQB1∗05:01. These TCCs were of different origin but expressed TCRs displaying the same amino acid sequences. They were activated through a hapten pathway; displayed CD45RO, CD28, PD-1, and CTLA-4 surface molecules; secreted the same panel of effector molecules as HLA class-I‒restricted TCCs; but displayed a lower capacity to lyse target cells. To conclude, DDS and DDS-NO interact with a number of HLA molecules to activate CD8+ TCCs, with HLA class-II‒restricted CD8+ TCCs that display hybrid CD4‒CD8 features also contributing to the promiscuous immune response that develops in patients.
author2 Ramathibodi Hospital
author_facet Ramathibodi Hospital
Qing Zhao
Mubarak Almutairi
Arun Tailor
Adam Lister
Nicolas Harper
James Line
Xiaoli Meng
Jirawat Pratoomwun
Kanoot Jaruthamsophon
Chonlaphat Sukasem
Yonghu Sun
Lele Sun
Monday O. Ogese
David J. MacEwan
Munir Pirmohamed
Jianjun Liu
David A. Ostrov
Hong Liu
Furen Zhang
Dean J. Naisbitt
format Article
author Qing Zhao
Mubarak Almutairi
Arun Tailor
Adam Lister
Nicolas Harper
James Line
Xiaoli Meng
Jirawat Pratoomwun
Kanoot Jaruthamsophon
Chonlaphat Sukasem
Yonghu Sun
Lele Sun
Monday O. Ogese
David J. MacEwan
Munir Pirmohamed
Jianjun Liu
David A. Ostrov
Hong Liu
Furen Zhang
Dean J. Naisbitt
author_sort Qing Zhao
title HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
title_short HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
title_full HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
title_fullStr HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
title_full_unstemmed HLA Class-II‒Restricted CD8<sup>+</sup> T Cells Contribute to the Promiscuous Immune Response in Dapsone-Hypersensitive Patients
title_sort hla class-ii‒restricted cd8<sup>+</sup> t cells contribute to the promiscuous immune response in dapsone-hypersensitive patients
publishDate 2022
url https://repository.li.mahidol.ac.th/handle/123456789/76019
_version_ 1763496682289364992