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Dimorphism in the T-cell receptor constant region affects T-cell function, phenotype and HIV outcome

Kaewpreedee, Prathanporna,b; Boonrat, Potcharab,c; Tansiri, Yadab,d; Rowland-Jones, Sarah L.e; Hansasuta, Pokratha,b,e

doi: 10.1097/QAD.0000000000002187
BASIC SCIENCE
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Objectives: CD8+ T cells recognize human leukocyte antigen-peptide complex through the T-cell receptor. Although amino acid variation in T-cell receptor variable chains often affects antigen specificity, dimorphism in the beta chain constant region (TRBC1 and TRBC2) is not thought to affect T-cell function. A recent study suggested that adoptive transfer of TRBC1-specific chimeric antigen-receptor-T cells provided an option for T-cell leukemia therapy that preserved T-cell immunity in the TRBC2 subset. This raises an important question as to whether TRBC1+T cells are qualitatively different from TRBC2+T cells.

Design: Cross-sectional study.

Methods: Sixty-six antiretroviral therapy-naive HIV-infected individuals, including 19 viraemic controllers and 47 noncontrollers, were enrolled. Peripheral blood mononuclear cells were isolated for T-cell functional assays, tetramer analyses, TRBC1 staining and immunophenotyping.

Results: Viraemic controllers had a higher proportion of circulating TRBC1+T cells than noncontrollers, raising the possibility that TRBC1+T cells might be associated with HIV control. TRBC1+T cells also showed more functional T-cell responses against both HIV and cytomegalovirus (P < 0.01). The immunophenotypes of TRBC1-bearing T cells were skewed towards naive and central memory phenotypes, whereas the majority of TRBC2-expressing T cells were terminally differentiated. Inverse correlations were observed between %TRBC1+T cells and HIV plasma viral load, which was most pronounced for CD8+ T cells (r = −0.7096, P = 0.00002357).

Conclusion: These data suggest that TRBC1+T-cell responses are of better quality than their TRBC2 counterparts, which should be considered in immunotherapeutic strategies for HIV infection. Conversely, depletion of TRBC1+T cells as part of the treatment of TRBC1+ T-cell malignancies may lead to compromised T-cell response quality.

aInterdisciplinary Program in Medical Microbiology, Graduate School, Chulalongkorn University

bDivision of Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital

cDepartment of Biology, Faculty of Science, Chulalongkorn University

dFaculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand

eNuffield Department of Medicine, NDM Research Building, University of Oxford, Old Road Campus, Oxford, UK.

Correspondence to Pokrath Hansasuta, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Rama IV Road, Pathumwan, Bangkok 10330, Thailand. E-mail: Pokrath.H@Chula.ac.th

Received 16 August, 2018

Revised 11 December, 2018

Accepted 21 December, 2018

Copyright © 2019 Wolters Kluwer Health, Inc.