Abstract

BackgroundT-cell receptor (TCR) repertoire development is an integral part of the adaptive immune response. T-cell activation requires recognition of appropriately processed antigens by the TCR. Development of a diverse repertoire of TCRs is therefore essential to ensure adequate protection from potential threats. The majority of T-cells in peripheral blood have TCRs composed of an alpha and a beta chain. At the DNA level, the TCR genes are formed through directed recombination from germline sequences—the so-called VDJ recombination [variable (V) joining (J) diversity (D) gene segments] which results in variations in the repertoire. The most variable part of TCRs is the Vβ region (VβTCR), which has multiple V segment families that can be quantitatively measured. However, only sparse data exists on the normal levels of the VβTCR repertoire in healthy children. We aimed to establish normal values for the VβTCR repertoire in atopic children without immunodeficiency.MethodsFifty-three children were recruited from food allergy, drug allergy, chronic urticaria and anaphylaxis registries and were divided into groups based on age: >0–2 years, 3–6 years, and 6–18 years. We used commercially available and fluorescently labeled antibodies against 21 human class-specific V segments of the TCRβ chain (Vβ) to study in peripheral blood the quantitative pattern of Vβ variation by flow cytometry.ResultsChildren of all ages exhibited a similar pattern of TCR Vβ expression. Vβ 2 was the most commonly expressed family in all three age groups [9.5 % (95 % CI, 8.9, 10 %), 8.8 % (95 % CI, 7.4, 10.2 %) and 7.6 % (7.0, 8.3 %) respectively]. However, the percentage of Vβ 2 decreased in older children and the percentage of Vβ 1 was higher in males. TCR Vβ expression in our sample of atopic children did not differ substantially from previously published levels in non-atopic cohorts.ConclusionTCR Vβ diversity follows a predictable and comparable pattern in atopic and healthy non-atopic children. Establishing normal levels for healthy children with and without atopy will contribute to a better definition of Vβ receptor deviation in children with primary immunodeficiency and/or immunodysregulation conditions.

Highlights

  • T-cell receptor (TCR) repertoire development is an integral part of the adaptive immune response

  • Since the discovery of the genetic background of the T-cell receptor (TCR), it is well known that the diversity and specificity of T-cells are a result of gene segment recombination

  • Our results reveal that Vβ 2 composed the majority of VβTCRs in our sample (Fig. 2)

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Summary

Introduction

T-cell receptor (TCR) repertoire development is an integral part of the adaptive immune response. The majority of T-cells in peripheral blood have TCRs composed of an alpha and a beta chain. At the DNA level, the TCR genes are formed through directed recombination from germline sequences—the so-called VDJ recombination [variable (V) joining (J) diversity (D) gene segments] which results in variations in the repertoire. There are four distinct T-cell antigen receptor polypeptides (α, β, γ, and δ), which form two different heterodimeric chains (α:β and γ:δ). This results in two subsets of T-cells (T-cell αβ and T-cell γδ) [2]. The most variable part of the TCR is the variable region of the β chain (Vβ)

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