Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection

Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems

Case Report: Textilome rénal à propos d\'un cas

No abstract available African Journal of Urology Vol.11(1) 2005:66-6

Épidémiologie des calculs urinaires dans le Sud de la France : étude rétrospective monocentrique

International audienceINTRODUCTION:Incidence of urolithiasis is increasing in industrialized countries. Amendments can be explained among others by dietary changes. More and more young patients have urolithiasis. The objective of this study was to analyze and update the epidemiology of stones in south of France about age and gender.MATERIAL AND METHODS:A retrospective single-center study from 2009 to June 2015 included all urolithiasis analyzed by infrared spectroscopy. Groups were composed according to the mineral content (oxalocalcic with whewellite and weddelite, calcium phosphate stones, uric acid stones…).RESULTS:A total of 749 stones were analyzed. The sex ratio was 1.96 all aged confused. The most common stones were oxalocalcic (51.3 %), followed mixed stones (21.2 %) and calcium phosphate stones (11.9 %). The calcium oxalate stones are mainly composed of whewellite (42 %) and calcium phosphate stones of carbapatite (18.6 %). The stones of whewellite were more frequent in men (P=0.0009), as well as uric acid stones (P=0.01) and mixed stones in women (P=0.00003), as well as calcium phosphate (P=0.0005).CONCLUSIONS:Epidemiology of stones has changed with an increased incidence in women, and nephrolithiasis patients getting older. A change in the type of stones is observed with increasing the proportion of mixed stones especially among women. Nutritional and metabolic studies are needed to find the etiology of the change in the epidemiology of urolithiasis.LEVEL OF EVIDENCE:4

Les facteurs pronostiques du cancer du rein. [Prognostic factors in renal cell carcinoma.]

International audienceIdentification of prognostic factors in renal cell carcinoma is very important today for three goals: providing patient information, giving appropriate treatments and selecting patients for adapted treatment schedules as well as new clinical trials. Prognostic factors in RCC include: anatomical (TNM classification), histological (Fuhrmann grade and histological subtype), clinical (symptoms and performance status) and molecular factors. For improving predicative accuracy of prognostic systems such as the TNM classification, new prognostic algorithms or nomograms have been designed combining independent prognostic variables. UISS and SSIGN are the 2 most effective prognostic systems within localized RCC. In metastatic disease, the two main systems that have been used for predicting response to immunotherapy are the model of the French Group of Immunotherapy and the Motzer model. With the arrivals of new molecular factors, these systems will perhaps have to evaluate: these new systems will require further validation as part of large prospective clinical trials

Motivations and personality characteristics of candidate sperm and oocyte donors according to parenthood status: a national study from the French CECOS network

International audienceAbstract STUDY QUESTION In a non-commercial national gamete donation programme, do the motivations and personality characteristics of candidate sperm and oocyte donors differ according to their parenthood status? SUMMARY ANSWER Moderate differences exist between non-parent and parent candidate donors in motivations for gamete donation and representations as well as in personality characteristics. WHAT IS KNOWN ALREADY Several studies have analysed the motivations and experiences of oocyte or sperm donors, but mainly in countries where gamete donation is a commercial transaction, and very few studies have reported results of personality traits using personality inventory tests. No study has specifically investigated the motivations and personality characteristics of candidate gamete donors according to parenthood status. STUDY DESIGN, SIZE, DURATION A prospective study was carried out including 1021 candidate donors from 21 centres (in university hospitals) of the national sperm and egg banking network in France between November 2016 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1021 candidate gamete donors were included in the study. During their first visit, male (n = 488) and female candidate donors (n = 533) completed a questionnaire on sociodemographic characteristics, their motivations for donation and their representations of donation, infertility and family. Secondly, a NEO Personality Inventory (NEO-PI-R) exploring the Big Five personality traits was completed online. Results were compared between parent and non-parent candidate donors. MAIN RESULTS AND THE ROLE OF CHANCE Altruistic values were the principal motive for donation irrespective of parenthood status. Reassurance about their fertility or preservation of sperm for future use was more often reported in non-parent than in parent candidate donors. With regard to representation of gamete donation or of the family, independently of their parenthood status, candidate donors more frequently selected social rather than biological representations. Mean personality characteristics were in the normal range. Non-parent candidate donors had higher scores on openness and depression than parents, while parent candidate donors appeared more social than non-parents. LIMITATIONS, REASONS FOR CAUTION The personality characteristics inventory was not completed by all candidate donors included in the study. However, family status did not differ between the two groups (NEO-PI-R completed (n = 525) or not), while the group who completed the NEO-PI-R had a higher educational level. This national study was performed in a country where gamete donation is subject to strict legislation. WIDER IMPLICATIONS OF THE FINDINGS In a global context where reproductive medicine is commercialized and gamete donor resources are limited, this study found that altruism and social representations of gamete donation and family are the main motivations for gamete donation in a country which prohibits financial incentive. These findings are relevant for health policy and for gamete donation information campaigns. STUDY FUNDING/COMPETING INTEREST(S) Grant from the Agence de la Biomédecine, France. The authors have nothing to disclose related to this study. TRIAL REGISTRATION NUMBER N/A