![haptens have immunogenicity but not reactivity haptens have immunogenicity but not reactivity](https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/attachment/20d710ab-0bcf-4851-9138-6b166dffc9c5/gr3_lrg.jpg)
Typical naive T cells express CD45RA, the co-stimulatory molecule CD27 in addition to lymph node-homing receptors CD62L and CCR7 ( 30). T cells surviving thymic selection have not yet encountered their cognate antigen, and hence are considered naive T cells ( 25) ( Figure 1). The overall outcome of the thymic selection is the maintenance of a T-cell repertoire that has sufficient, but not too strong, affinity for any self-pMHC complex ( 29). This discrepancy is explained by thymic selection where the fate of T-cell precursors is dependent on the recognition of self-peptides (self-p) presented by MHC molecules on thymic stromal cells ( 28). Hence, TCR repertoire estimation vastly outnumbers the actual diversity of a person’s TCR repertoire ( 27). Nevertheless, there are only an estimated 10 12 T cells in the human body ( 26). Indeed, T-cell precursors randomly and imprecisely rearrange V and J segments of the TCR alpha and V, D, and J segments of the TCR beta chains to create a complete TCR.Įstimation of the TCR repertoire diversity ranges from > 10 20 ( 23) to 10 61 ( 24, 25).
![haptens have immunogenicity but not reactivity haptens have immunogenicity but not reactivity](https://file.scirp.org/Html/paperimages/2327_5.jpg)
It is now clear that the ability of T cells to promote an effective immune response depends on a large repertoire of unique T-cell receptors (TCRs) generated and selected in the thymus. The identification of lymphocytes as the main cell type responsible for both cellular and humoral immunity started in the early 1950s with the emergence of cell culture techniques. We provide an overview of the data supporting different models of T-cell recognition of drugs and chemicals and discuss speculative models addressing the origin of drug/chemical responsive naive T cells. The aim of this review is to describe the role of the naive T-cell repertoire in drug and chemical allergy. However, attention has recently turned to the naive T-cell repertoire, since it may largely determine the efficacy of the induced immune response ( 22). Most studies have focused on the identification of memory T cells that recognize drugs/chemicals and the insights obtained have led to the development of allergy diagnostic tests ( 7– 21). On the other hand, T cells constitute the main pathogenic effector cells in delayed hypersensitivity reactions ( 4– 6). On one hand, drug-specific T cells provide the necessary help for mounting an effective B-cell response observed in immediate-type hypersensitivity reactions. T cells are central to allergic reactions. The consequences of drug and chemical allergy can be severe, including systemic adverse effects ( 1– 3). Up to one third of ADRs are attributable to unpredictable drug hypersensitivity mediated by an adaptive immune response and named drug allergy. Understanding this role has the potential to reveal efficient strategies not only for allergy diagnosis but also for prediction of the immunogenic potential of new chemicals.Īdverse drug reactions (ADRs) are a major public health problem. The aim of this review is to address the existence and the role of a naive T-cell repertoire in drug and chemical allergy. These observations may also suggest that in the case of drug/chemical allergy, the T-cell repertoire results from particular properties of certain TCR to recognize hapten-modified peptides without need for previous thymic selection. Recent observations raise the hypothesis that not only the drug/chemical, but also parts of the haptenated protein or peptides may constitute the important structural determinants for antigen recognition by the TCR. On the other hand, a large T-cell repertoire found in multiple donors would underline the potential of a drug/chemical to be recognized by many donors. Selection of drug/chemical-specific T cells could be a relatively rare event accounting for the low occurrence of drug allergy. Due to the artificial nature of drug/chemical-T-cell epitopes, it is not clear whether thymic selection of drug/chemical-specific T cells is a common phenomenon or remains limited to few donors or simply does not exist, suggesting T-cell receptor (TCR) cross-reactivity with other antigens. During thymic selection, T cells that have not yet encountered their cognate antigen are considered naive T cells. 2 Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, INSERM, Châtenay-Malabry, FranceĪllergic reactions to drugs and chemicals are mediated by an adaptive immune response involving specific T cells.1Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States.Rami Bechara 1, Alexia Feray 2 and Marc Pallardy 2*