SummaryReeent studies have demonstrated that the CD3-~ subunlt of the T eell antigen reeeptor (TCR) eomplex Is involved In signal transduetlon. However, the funetlon of the remalnlng Invariant subunits, CD3-y, -ö, and e, Is still poorly understood. To examine thelr role In TCR funetlon, we have eonstrueted TCR/CD3 eomplexes devold of tunetlonal ~ subunlt and showed that they are still able to trigger the produellon of Interleukln-2 in response to antigen or superantigen. These data, together with previous results, Indleate that the TCR/ CD3 eomplex Is eomposed of at least two parallel Iransduelng unlts, made 01 the YÖE and ~ ehalns, respeetlvely, Furthermore, the analysis 01 partially truneated ~ ehains has led us to Indlvlduallze a lunetlonal domaln that may have eonstltuted the buildlng block of most of the transduelng subunlts assoelated wlth antigen reeeptors and some Fe receptors. IntroduetionThe T cell antigen receptor (TCR) is a multisubunit complex composed of the products of at least six distinct genes. The TCR a and TCR ß subunits exist as disulfidelinked heterodimers, possess short cytoplasmic tails, and contain clonally variable regions that determine the antigenic specificity of the complex. The remaining subunits, termed CD3-y, -ö, -E, -~, and -1], are invariant, noncovalently associated with the TCR aß dimer, and possess large intracytoplasmic domains thought to be responsible for coupling antigen recognition to various signal transductlon pathways. The evolutionarily related y, Ö, and e subunits are expressed as noncovalently associated ye and OE pairs (Koning et al., 1990;Blumberg et al. , 1990; De la Herra et al. , 1991), and display immunoglobulin-like extracellular domains (Gold et al., 1987). In contrast, the ~ and 1] subunlts contaln an extracellular domain of only 9 residues and constitute the prototype of a new protein family that includes the y chain of the high affinity IgE receptor (FceRI)

Nanotechnology and more particularly nanotechnology-based products and materials have provided a huge potential for novel solutions to many of the current challenges society is facing. However, nanotechnology is also an area of product innovation that is sometimes developing faster than regulatory frameworks. This is due to the high complexity of some nanomaterials, the lack of a globally harmonised regulatory definition and the different scopes of regulation at a global level. Research organisations and regulatory bodies have spent many efforts in the last two decades to cope with these challenges. Although there has been a significant advancement related to analytical approaches for labelling purposes as well as to the development of suitable test guidelines for nanomaterials and their safety assessment, there is a still a need for greater global collaboration and consensus in the regulatory field. Furthermore, with growing societal concerns on plastic litter and tiny debris produced by degradation of littered plastic objects, the impact of micro- and nanoplastics on humans and the environment is an emerging issue. Despite increasing research and initial regulatory discussions on micro- and nanoplastics, there are still knowledge gaps and thus an urgent need for action. As nanoplastics can be classified as a specific type of incidental nanomaterials, current and future scientific investigations should take into account the existing profound knowledge on nanotechnology/nanomaterials when discussing issues around nanoplastics. This review was conceived at the 2019 Global Summit on Regulatory Sciences that took place in Stresa, Italy, on 24–26 September 2019 (GSRS 2019) and which was co-organised by the Global Coalition for Regulatory Science Research (GCRSR) and the European Commission's (EC) Joint Research Centre (JRC). The GCRSR consists of regulatory bodies from various countries around the globe including EU bodies. The 2019 Global Summit provided an excellent platform to exchange the latest information on activities carried out by regulatory bodies with a focus on the application of nanotechnology in the agriculture/food sector, on nanoplastics and on nanomedicines, including taking stock and promoting further collaboration. Recently, the topic of micro- and nanoplastics has become a new focus of the GCRSR. Besides discussing the challenges and needs, some future directions on how new tools and methodologies can improve the regulatory science were elaborated by summarising a significant portion of discussions during the summit. It has been revealed that there are still some uncertainties and knowledge gaps with regard to physicochemical properties, environmental behaviour and toxicological effects, especially as testing described in the dossiers is often done early in the product development process, and the material in the final product may behave differently. The harmonisation of methodologies for quantification and risk assessment of nanomaterials and micro/nanoplastics, the documentation...

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