Dataset Information

Effector V?9V?2 T cells dominate the human fetal ?? T-cell repertoire.

ABSTRACT: ?? T cells are unconventional T cells recognizing antigens via their ?? T-cell receptor (TCR) in a way that is fundamentally different from conventional ?? T cells. ?? T cells usually are divided into subsets according the type of V? and/or V? chain they express in their TCR. T cells expressing the TCR containing the ?-chain variable region 9 and the ?-chain variable region 2 (V?9V?2 T cells) are the predominant ?? T-cell subset in human adult peripheral blood. The current thought is that this predominance is the result of the postnatal expansion of cells expressing particular complementary-determining region 3 (CDR3) in response to encounters with microbes, especially those generating phosphoantigens derived from the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid synthesis. However, here we show that, rather than requiring postnatal microbial exposure, V?9V?2 T cells are the predominant blood subset in the second-trimester fetus, whereas V?1(+) and V?3(+) ?? T cells are present only at low frequencies at this gestational time. Fetal blood V?9V?2 T cells are phosphoantigen responsive and display very limited diversity in the CDR3 of the V?9 chain gene, where a germline-encoded sequence accounts for >50% of all sequences, in association with a prototypic CDR3?2. Furthermore, these fetal blood V?9V?2 T cells are functionally preprogrammed (e.g., IFN-? and granzymes-A/K), with properties of rapidly activatable innatelike T cells. Thus, enrichment for phosphoantigen-responsive effector T cells has occurred within the fetus before postnatal microbial exposure. These various characteristics have been linked in the mouse to the action of selecting elements and would establish a much stronger parallel between human and murine ?? T cells than is usually articulated.

SUBMITTER: Dimova T

PROVIDER: S-EPMC4330771 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire.

Dimova Tanya T Brouwer Margreet M Gosselin Françoise F Tassignon Joël J Leo Oberdan O Donner Catherine C Marchant Arnaud A Vermijlen David D

Proceedings of the National Academy of Sciences of the United States of America 20150123 6

γδ T cells are unconventional T cells recognizing antigens via their γδ T-cell receptor (TCR) in a way that is fundamentally different from conventional αβ T cells. γδ T cells usually are divided into subsets according the type of Vγ and/or Vδ chain they express in their TCR. T cells expressing the TCR containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2 T cells) are the predominant γδ T-cell subset in human adult peripheral blood. The current thought is that this p ...[more]

PMID: 25617367

Similar Datasets

Project description:Cytomegalovirus (CMV) infection elicits a strong T-cell immune response, which increases further during aging in a process termed "memory inflation." CMV downregulates the expression of HLA-A and HLA-B on the surface of infected cells to limit presentation of viral peptides to T-cells although HLA-C is relatively spared as it also engages with inhibitory killer immunoglobulin receptor receptors and therefore reduces lysis by natural killer cells. We investigated the magnitude and functional properties of CMV-specific CD8+ T-cells specific for 10 peptides restricted by HLA-C in a cohort of 53 donors between the age of 23 and 91?years. This was achieved via peptide stimulation of PBMCs followed by multicolor flow cytometry. Three peptides, derived from proteins generated in the immediate-early period of viral replication and restricted by HLA-Cw*0702, elicited strong immune responses, which increased substantially with age such that the average aggregate response represented 37% of the CD8+ T-cell pool within donors above 70?years of age. Remarkably, a single response represented 70% of the total CD8+ T-cell pool within a 91-year-old donor. HLA-Cw*0702-restricted CD8+ T-cell responses were immunodominant over HLA-A and HLA-B-restricted CMV-specific responses and did not show features of exhaustion such as PD-1 or CD39 expression. Indeed, such CTL exhibit a polyfunctional cytokine profile with co-expression of IFN-? and TNF-? and a strong cytotoxic phenotype with intracellular expression of perforin and granzymeB. Functionally, HLA-Cw*0702-restricted CTL show exceptionally high avidity for cognate peptide-HLA and demonstrate very early and efficient recognition of virally infected cells. These observations indicate that CD8+ T-cells restricted by HLA-C play an important role in the control of persistent CMV infection and could represent a novel opportunity for CD8+ T-cell therapy of viral infection within immunosuppressed patients. In addition, the findings provide further evidence for the importance of HLA-C-restricted T-cells in the control of chronic viral infection.

Dataset Information

Effector V?9V?2 T cells dominate the human fetal ?? T-cell repertoire.

Publications

Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure