Direct Recognition Research Articles

Turn-off fluorescent nanoprobe based on carbon dots synthesised by UV/H2O2 advanced oxidation for the detection of bisphenol A in canned foods.

Anovel assay was developedbased on a turn-off fluorescent probe using the in situ generation of carbon dots (CDs) by means of UV/H2O2 advanced oxidation of carbohydrates for the detection of bisphenol A (BPA) in food. Different parameters involved in the synthesis of CDs for the direct recognition of BPA have been optimised and a sensing mechanism is outlined. The presence of H2O2 during CD synthesis causes a fluorescence enhancement due to the action of highly oxidant HO· radicals formed throughout the photochemical reaction. Phenolic compounds such as BPA can be easily degraded by the UV/H2O2 oxidation process, acting as a HO· free radical scavengers. This results in a decrease in the fluorescence that can be related to the BPA concentration. Under optimal conditions, a detection limit of 15µg/kg of BPA and a quantification limit of 46µg/kg of BPA in food sampleswere obtained. The repeatability and reproducibility, expressed as relative standard deviation and obtained for two concentration levels (30µg/kg and 200µg/kg, n = 5), were less than 2.0% and 6.4%, respectively. The proposed procedure was applied to the analysis of five samples of canned foods (sweet corn, peas, mushrooms, cockles and natural tuna), obtaining concentrations in the range 29.8-49.9µg/kg of sample. Recovery studies were conducted at two concentration levels (100and 400µgBPA/kg of sample), resulting in recoveries in the range 99-101%. Method validation against two certified reference materials was also successfully performed. The experimental results demonstrate that the novel approach is suitable for the detection and quantification of BPA in canned foods.

Direct recognition of an intact foreign protein by an αβ T cell receptor

αβ T cell receptors (αβTCRs) co-recognise antigens when bound to Major Histocompatibility Complex (MHC) or MHC class I-like molecules. Additionally, some αβTCRs can bind non-MHC molecules, but how much intact antigen reactivities are achieved remains unknown. Here, we identify an αβ T cell clone that directly recognises the intact foreign protein, R-phycoerythrin (PE), a multimeric (αβ)6γ protein complex. This direct αβTCR–PE interaction occurs in an MHC-independent manner, yet triggers T cell activation and bound PE with an affinity comparable to αβTCR–peptide–MHC interactions. The crystal structure reveals how six αβTCR molecules simultaneously engage the PE hexamer, mediated by the complementarity-determining regions (CDRs) of the αβTCR. Here, the αβTCR mainly binds to two α-helices of the globin fold in the PE α-subunit, which is analogous to the antigen-binding platform of the MHC molecule. Using retrogenic mice expressing this TCR, we show that it supports intrathymic T cell development, maturation, and exit into the periphery as mature CD4/CD8 double negative (DN) T cells with TCR-mediated functional capacity. Accordingly, we show how an αβTCR can recognise an intact foreign protein in an antibody-like manner.

PENGENALAN ALAT TRANSPORTASI KERETA API PADA ANAK USIA DINI

Early childhood education is the main education towards higher education. Early childhood education must pay attention to the maturity of children in all aspects of life. Knowledge and understanding of something can be instilled into early childhood by various methods. In instilling understanding in children through direct recognition so that children will be stimulated through hearing (auditory) and sight (visual). The introduction of means of transportation is usually an attraction in itself for early childhood. Transportation tools become easy to understand because they are often seen even using these means of transportation. The introduction of means of transportation is carried out through auditory, visual and psychomotor. Improved auditory and visual abilities are obtained by the method of telling stories about trains. Videos are also shown to facilitate the child's understanding. Increasing children's knowledge and psychomotor using field trips directly by train to gain experience

A Photoelectrochemical Biosensor Mediated by CRISPR/Cas13a for Direct and Specific Detection of MiRNA-21.

Direct detection of miRNA is currently limited by the complex amplification and reverse transcription processes of existing methods, leading to low sensitivity and high operational demands. Herein, we developed a CRISPR/Cas13a-mediated photoelectrochemical (PEC) biosensing platform for direct and sensitive detection of miRNA-21. The direct and specific recognition of target miRNA-21 by crRNA-21 eliminates the need for pre-amplification and reverse transcription of miRNA-21, thereby preventing signal distortion and enhancing the sensitivity and precision of target detection. When crRNA-21 binds to miRNA-21, it activates the trans-cleavage activity of CRISPR/Cas13a, leading to the non-specific cleavage of biotin-modified DNA with uracil bases (biotin-rU-DNA). This cleavage prevents the biotin-rU-DNA from being immobilized on the electrode surface. As a result, streptavidin cannot attach to the electrode via specific biotin binding, reducing spatial resistance and causing a positively correlated increase in the photocurrent response. This Cas-PEC biosensor has good analytical capabilities, linear responses between 10 fM and 10 nM, a minimum detection limit of 9 fM, and an excellent recovery rate in the analysis of real human serum samples. This work presented an innovative solution for detecting other biomarkers in bioanalysis and clinical diagnostics.

Identification and function of microRNAs in hemipteran pests: A review.

Hemiptera is one of the most significant orders of insect pests, including whiteflies, true bugs, aphids, planthoppers, psyllids, and so forth, which have led to substantial economic losses in agricultural industries and have significantly affected food yields through their ability to suck the phloem sap of crops and transmit numerous bacterial and viral pathogens. Therefore, explorations of pest-specific, eco-friendly and easy-to-adopt technologies for hemipteran pest control are urgently needed. To the best of our knowledge, microRNAs (miRNAs), which are endogenous non-coding small RNAs approximately 22 nucleotides in length, are involved in regulating gene expression via the direct recognition and binding of the 3'-untranslated region (3'-UTR) of target messenger RNAs (mRNAs) or by acting as a center of a competitive endogenous RNA (ceRNA) network at the post-transcriptional level. This review systematically outlines the characterization and functional investigation of the miRNA biogenesis pathway in hemipteran pests, such as whiteflies, true bugs, aphids and planthoppers. In addition, we explored the results of small RNA sequencing and functional observations of miRNAs in these pests, and the results suggest that the numerous miRNAs obtained and annotated via high-throughput sequencing technology and bioinformatic analyses contribute to molting development, fitness, wing polyphenism, symbiont interactions and insecticide resistance in hemipteran pests. Finally, we summarize current advances and propose a framework for future research to extend the current data and address potential limitations in the investigation and application of hemipteran miRNAs.

FBXO38 is dispensable for PD-1 regulation

SKP1-CUL1-F-box protein (SCF) ubiquitin ligases are versatile protein complexes that mediate the ubiquitination of protein substrates. The direct substrate recognition relies on a large family of F-box-domain-containing subunits. One of these substrate receptors is FBXO38, which is encoded by a gene found mutated in families with early-onset distal motor neuronopathy. SCFFBXO38 ubiquitin ligase controls the stability of ZXDB, a nuclear factor associated with the centromeric chromatin protein CENP-B. Loss of FBXO38 in mice results in growth retardation and defects in spermatogenesis characterized by deregulation of the Sertoli cell transcription program and compromised centromere integrity. Moreover, it was reported that SCFFBXO38 mediates the degradation of PD-1, a key immune-checkpoint inhibitor in T cells. Here, we have re-addressed the link between SCFFBXO38 and PD-1 proteolysis. Our data do not support the notion that SCFFBXO38 directly or indirectly controls the abundance and stability of PD-1 in T cells.

A high-precision localization method for underwater targets incorporating direct path recognition and sound rays bending compensation

A high-precision localization method for underwater targets incorporating direct path recognition and sound rays bending compensation

Genetics and Epigenetics of Type 1 Diabetes Self-Reactive T Cells.

Type 1 diabetes (T1D) serves as an exemplar of chronic autoimmune disease characterized by insulin deficiency due to pancreatic β-cell destruction, leading to hyperglycemia and progressive organ failure. Until recently, therapeutic efforts to mitigate the root cause of disease have been limited by the challenges in studying mechanisms involved in immune tolerance in humans. The current clinical advances, and existing challenges, highlight a need to incorporate new insights into mechanisms into correlative studies that assess immune tolerance in the setting of delayed β-cell destruction. Among several factors known to promote T1D, autoreactive T cells play a critical role in initiating and sustaining disease through their direct recognition and destruction of β cells. Emerging research defining the genetic and epigenetic etiology of long-lived β-cell-specific T cells is providing new insight into mechanisms that promote lifelong disease and future opportunities for targeted therapeutic intervention. This article will provide an overview of recent progress toward understanding the development of autoreactive T cells and epigenetic mechanisms stabilizing their developmental state during T1D pathogenesis.

Terahertz spoof plasmonic neural network for diffractive information recognition and processing

All-optical diffractive neural networks, as analog artificial intelligence accelerators, leverage parallelism and analog computation for complex data processing. However, their low space transmission efficiency or large spatial dimensions hinder miniaturization and broader application. Here, we propose a terahertz spoof plasmonic neural network on a planar diffractive platform for direct multi-target recognition. Our approach employs a spoof surface plasmon polariton coupler array to construct a diffractive network layer, resulting in a compact, efficient, and easily integrable architecture. We designed three schemes: basis vector classification, multi-user recognition, and MNIST handwritten digit classification. Experimental results reveal that the terahertz spoof plasmonic neural network successfully classifies basis vectors, recognizes multi-user orientation information, and directly processes handwritten digits using a designed input framework comprising a metal grating array, transmitters, and receivers. This work broadens the application of terahertz plasmonic metamaterials, paving the way for terahertz on-chip integration, intelligent communication, and advanced computing systems.

Impedimetric identification of heteroMOFs modified porous nickel foam self-supports as robust electrodes for CA 19-9 pancreatic tumor marker in human serum

An impedance-based electrochemical immunosensor for direct and binder-free target recognition of carbohydrate antigen (CA 19-9) tumor biomarker for the early diagnosis of pancreatic cancer was reported. This study uses an in situ solvothermal process to develop a simple method for the one-pot construction of Ni-Fe heteroMOFs (HFNMOFs,) self-supported on conductive nickel foam (NicFm). Utilizing HFNMOFs@NicFm developed in this study, the electrochemical performance of the biosensor was studied for the first time. The as-prepared mixed MOFs decorated NicFm electrodes displayed potential electrochemical outputs. They demonstrated the potential for developing binder-free non-enzymatic immunosensors with wide linear limits, high selectivity, stability, and excellent sensitivity. The bifunctional MOFs exhibit improved electrochemical conductivity owing to the highly exposed metal sites and hierarchical porosity. The changes in the charge transfer resistance present a linear response against increasing target concentrations. The immunosensor developed in this study exhibited its detection limit of 2.56 U/mL. Further, the bioelectrodes produced were validated against real human spiked serum with good results of percentage recovery, indicating the immunosensor is well-suitable to be tested in real-time analysis.

Direct electromagnetic information processing with planar diffractive neural network.

Diffractive neural network in electromagnetic wave-driven system has attracted great attention due to its ultrahigh parallel computing capability and energy efficiency. However, recent neural networks based on the diffractive framework still face the bottlenecks of misalignment and relatively large size limiting their further applications. Here, we propose a planar diffractive neural network (pla-NN) with a highly integrated and conformal architecture to achieve direct signal processing in the microwave frequency. On the basis of printed circuit fabrication process, the misalignment could be effectively circumvented while enabling flexible extension for multiple conformal and stacking designs. We first conduct validation on the fashion-MNIST dataset and experimentally build up a system using the proposed network architecture for direct recognition of different geometry structures in the electromagnetic space. We envision that the presented architecture, once combined with the advanced dynamic maneuvering techniques and flexible topology, would exhibit unlimited potentials in the areas of high-performance computing, wireless sensing, and flexible wearable electronics.

Ultrasound wavelet spectra enable direct tissue recognition and full-color visualization

Traditional brightness-mode ultrasound imaging is primarily constrained by the low specificity among tissues and the inconsistency among sonographers. The major cause is the imaging method that represents the amplitude of echoes as brightness and ignores other detailed information, leaving sonographers to interpret based on organ contours that depend highly on specific imaging planes. Other ultrasound imaging modalities, color Doppler imaging or shear wave elastography, overlay motion or stiffness information to brightness-mode images. However, tissue-specific scattering properties and spectral patterns remain unknown in ultrasound imaging. Here we demonstrate that the distribution (size and average distance) of scattering particles leads to characteristic wavelet spectral patterns, which enables tissue recognition and high-contrast ultrasound imaging. Ultrasonic wavelet spectra from similar particle distributions tend to cluster in the eigenspace according to principal component analysis, whereas those with different distributions tend to be distinguishable from one another. For each distribution, a few wavelet spectra are unique and act as a fingerprint to recognize the corresponding tissue. Illumination of specific tissues and organs with designated colors according to the recognition results yields high-contrast ultrasound imaging. The fully-colorized tissue-specific ultrasound imaging potentially simplifies the interpretation and promotes consistency among sonographers, or even enables the applicability for non-professionals.

The Effect of Personal Color Perception on Makeup Behavior of Female College Students in Their 20s

In the modern era, as the era of external image communication, interest in appearance has become an essential factor in success. As such, many people are investing a lot of time and money in appearance management to create an ideal image. In particular, personal color occupies a large proportion as a field of image management. The purpose of this study was to find out the personal color recognition and the perception of makeup behavior according to personal color in female college students in their 20s. As a result of the study, the overall personal color recognition and makeup behavior of the pre-survey group were high. Direct recognition, preference recognition, and external advice by sub-factors of personal color recognition of the pre-survey group were found to have a statistically significant positive (+) correlation with aesthetics, fashionability, interest, co-movement, courtesy by sub-factors of makeup behavior. As a result of the pre-post analysis of the subject’s personal color recognition, it was found that the post-mortem of personal color recognition was higher than before, showing a statistically significant difference. This study was intended to empirically investigate whether it affects personal color perception and makeup behavior, self-esteem, and interpersonal relationships among female college students in their 20s, and present it as basic data necessary to enhance the changed social atmosphere and lead beauty trends. The limitation of this study is that it is difficult to generalize the results only to 155 female college students at K University, so subsequent studies should expand the region, research subject, and major.

Perceptions of transanal total mesorectal excision surgical quality and patient screening

As a rapid developing rectal cancer procedure that has been in existence for more than a decade, transanal total mesorectal excision (taTME) has had a rough experience along the way, suggesting the importance of improving its surgical quality. In the current view of quality control of taTME, its main advantages are that it could increase the distance of distal margins, reduce the positive rate of circumferential margins, and improve the quality of total mesorectal excision. As few high-quality clinical studies have been conducted, the limitations brought about by confounding bias and publication bias that could not be excluded in current published studies call for a cautious interpretation of the current conclusions. At this stage taTME is only recommended in highly selective patients and centers. Under these circumstances, we aim to discuss the quality assessment of the taTME procedure and the selection of patients and centers. Based on current evidence and practical experience, we typically select patients with difficult pelvis, low rectal cancer, and/or those requiring direct visual recognition of the distal margin after neoadjuvant chemoradiation to perform taTME in our center.

THE VIEW FROM THE EAST ON THE PROBLEM FIELD OF WESTERN LITERARY AND THEORETICAL STU

The study aims to determine the status of modern theoretical literary debate within the context of scientific theorizing in China and Japan. Growing understanding of the crisis of Euro-Atlantic literary-theoretical thought in the first two decades of the 21st century took shape in the publication of works by venerable specialists in the field of literary studies devoted to the causes of its occurrence and the taxonomy of directions and theoretical tools to overcome it. What unites this whole corpus of extensive research is an indirect or direct recognition of the decline of productive literary theoretical research, which came after the literary theoretical breakthrough of the late 60s of the 20th century. At the same time, the refusal to recognize Western literature as a model, artistic and aesthetic norm caused the emergence of powerful voices of authors whose writings are not directly shaped by the Western literary canon. Simultaneously, the refusal to recognize Western literature as a model, artistic and aesthetic norm caused the emergence of powerful voices of writers whose work is not directly shaped by the Western literary canon. The polemic started with the postcolonial discourse regarding the epistemological perspectives of Western literary theory in a situation of clash with a non-Western literary text, which, at the turn of the 21st century, developed into a reflection of its ontological potential. Both intellectuals and artists of the age of Multiculturalism, who relied on the Poststructuralist “breakthrough to the transcendental” on the one hand and on the philosophical nature as well as poetics and aesthetics of art of the East on the other, demonstrated that a complex of issues related to the future existence of literary theory risen by the literature itself, is much more sophisticated. First of all, these processes are caused by the early formation of new future horizons of world literature, in which artists with Eastern artistic and aesthetic background and knowledge play a major role. Following the mastering of the Western literary and aesthetic canon – rather a long period when the writings of these authors were derived from the general paradigm of Western literature – the formation of a new literature takes place, protesting Bhabha’s idea of mimicry as a way of survival and adaptation of the colonized and demonstrating the non-Western canon as its artistic source. The era of posttheory should testify that the rumours of the “death of the theory” may be greatly exaggerated in case the overcoming crisis of theory, which is based on literary knowledge originating from the East.

Powdery mildew effectors AVRA1 and BEC1016 target the ER J-domain protein HvERdj3B required for immunity in barley.

The barley powdery mildew fungus, Blumeria hordei (Bh), secretes hundreds of candidate secreted effector proteins (CSEPs) to facilitate pathogen infection and colonization. One of these, CSEP0008, is directly recognized by the barley nucleotide-binding leucine-rich-repeat (NLR) receptor MLA1 and therefore is designated AVRA1. Here, we show that AVRA1 and the sequence-unrelated Bh effector BEC1016 (CSEP0491) suppress immunity in barley. We used yeast two-hybrid next-generation interaction screens (Y2H-NGIS), followed by binary Y2H and in planta protein-protein interactions studies, and identified a common barley target of AVRA1 and BEC1016, the endoplasmic reticulum (ER)-localized J-domain protein HvERdj3B. Silencing of this ER quality control (ERQC) protein increased Bh penetration. HvERdj3B is ER luminal, and we showed using split GFP that AVRA1 and BEC1016 translocate into the ER signal peptide-independently. Overexpression of the two effectors impeded trafficking of a vacuolar marker through the ER; silencing of HvERdj3B also exhibited this same cellular phenotype, coinciding with the effectors targeting this ERQC component. Together, these results suggest that the barley innate immunity, preventing Bh entry into epidermal cells, requires ERQC. Here, the J-domain protein HvERdj3B appears to be essential and can be regulated by AVRA1 and BEC1016. Plant disease resistance often occurs upon direct or indirect recognition of pathogen effectors by host NLR receptors. Previous work has shown that AVRA1 is directly recognized in the cytosol by the immune receptor MLA1. We speculate that the AVRA1 J-domain target being inside the ER, where it is inapproachable by NLRs, has forced the plant to evolve this challenging direct recognition.

Vis-NIR spectroscopic discriminant analysis of aflatoxin B1 excessive standard in peanut meal as feedstuff materials

A fast, simple and reagent-free detection method for aflatoxin B1 (AFB1) is of great significance to food safety and human health. Visible and near-infrared (Vis-NIR) spectroscopy was applied to the discriminant analysis of AFB1 excessive standard of peanut meal as feedstuff materials. Two types of excessive standard discriminant models based on spectral quantitative analysis with partial least squares (PLS) and direct pattern recognition with partial least squares-discrimination analysis (PLS-DA) were established, respectively. Multi-parameter optimization of Norris derivative filtering (NDF) was used for spectral preprocessing; the two-stage wavelength screening method based on equidistant combination-wavelength step-by-step phase-out (EC-WSP) was used for wavelength optimization. A rigorous sample experimental design of calibration-prediction-validation was utilized. The calibration and prediction samples were used for modeling and parameter optimization, and the selected model was validated using the independent validation samples. For quantitative analysis-based, the positive, negative and total recognition-accuracy rates in validation (RARV+, RARV-, and RARV) were 84.8 %, 74.6 % and 79.8 %, respectively; but, the relative root mean square error of prediction was as high as 51.0 %. For pattern recognition-based, the RARV+, RARV-, and RARV were 93.3 %, 90.5 % and 91.9 %, respectively. Moreover, the number of wavelengths N was drastically reduced to 17, and the discrete wavelength combination was in NIR overtone frequency region. The results indicated that, the EC-WSP-PLS-DA model achieved significantly better discrimination effect. Thus demonstrated that Vis-NIR spectroscopy has feasibility for the excessive standard discrimination of aflatoxin B1 in feedstuff materials.

Protective effect of melatonin on imidacloprid-induced pyroptosis and ferroptosis by mediating peptidoglycan in the gut of the common carp (Cyprinus carpio)

Imidacloprid (IMI) is a contaminant widespread in surface water, causing serious intestinal damage in the common carp. Melatonin (MT), an endogenous indoleamine hormone, plays a crucial role in mitigating pesticide-induced toxicity. Our previous research has demonstrated that MT effectively reduces the production of intestinal microbial-derived signal peptidoglycan (PGN) induced by IMI, thereby alleviating intestinal tight junction injuries in the common carp. In this study, we performed a transcriptomic analysis to explore the effect of MT on the IMI exposure-induced gut damage of the common carp. The results elucidated that the ferroptosis, mitogen-activated protein kinases (MAPKs), and nucleotide oligomerization domain (NOD)-like signaling pathways were significantly associated with IMI exposure and MT treatment. Meanwhile, the exposure to IMI resulted in the formation of pyroptotic bodies and distinct morphological features of ferroptosis, both mitigated with the addition of MT. Immunofluorescence double staining demonstrated that MT abolished the elevated expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Gasdermin D (GSDMD) induced by IMI, as well as reduced expression of ferritin heavy chains (FTH) and glutathione peroxidase 4 (GPX4) in gut tissues. Subsequently, we found that the exposure to IMI or PGN enhanced the expression of toll-like receptors (TLR) 2 (a direct recognition receptor of PGN) triggering the P38MAPK signaling pathway, thereby aggravating the process of pyroptosis and ferroptosis of cell models. The addition of MT or SB203580 (a P38MAPK inhibitor) significantly reduced pyroptotic cells, and also decreased iron accumulation. Consequently, these results indicate that MT alleviates IMI-induced pyroptosis and ferroptosis in the gut of the common carp through the PGN/TLR2/P38MAPK pathway.

A deep learning approach for Direct Immunofluorescence pattern recognition of Autoimmune Bullous Diseases.

Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning to enhance disease management. Dermatology has seen improved diagnostics, particularly in skin cancer detection, through the integration of AI. However, the potential of AI in automating immunofluorescence imaging for autoimmune bullous skin diseases remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of deep learning to automatically classify DIF patterns, including the Intercellular Pattern (ICP) and the Linear Pattern (LP), holds promise for improving the diagnosis of autoimmune bullous skin diseases. The objectives of this study are to develop AI algorithms for automated classification of autoimmune bullous skin disease DIF patterns, such as ICP and LP. This aims to enhance diagnostic accuracy, streamline disease management, and improve patient outcomes through deep learning-driven immunofluorescence interpretation. We collected immunofluorescence images from skin biopsies of patients suspected of AIBD between January 2022 and January 2024. Skin tissue was obtained via 5-mm punch biopsy, prepared for direct immunofluorescence. Experienced dermatologists classified the images into three classes: ICP, LP, and negative. To evaluate our deep learning approach, we divided the images into training (436) and test sets (93). We employed transfer learning with pre-trained deep neural networks and conducted 5-fold cross-validation to assess model performance. Our dataset's class imbalance was addressed using weighted loss and data augmentation strategies. The models were trained for 50 epochs using Pytorch, achieving an image size of 224x224 for both CNNs and the Swin Transformer. Our study compared six CNNs and the Swin transformer for AIBDs image classification, with the Swin transformer achieving the highest average validation accuracy of 98.5%. On a separate test set, the best model attained an accuracy of 94.6%, demonstrating 95.3% sensitivity and 97.5% specificity across AIBDs classes. Visualization with Grad-CAM highlighted the model's reliance on characteristic patterns for accurate classification. The study highlighted CNN's accuracy in identifying DIF features. This approach aids automated analysis and reporting, offering reproducibility, speed, data handling, and cost-efficiency. Integrating deep learning in skin immunofluorescence promises precise diagnostics and streamlined reporting in this branch of dermatology.

Abstract LB073: Adoptive transfer of one CD4TCR and one CD8TCR targeting autochthonous neoantigens are essential and sufficient for eradication of naturally heterogeneous solid tumors

Abstract Despite advances in checkpoint blockade therapy or adoptive transfer of tumor-infiltrating lymphocytes (TILs), achieving cure remains challenging, but success of immunotherapy seems to depend on recognition of tumor-specific antigens (neoantigens). We aimed to determine how many neoantigens need to be recognized by how many different TCRs for eradication of solid tumors. Unmanipulated, naturally expressed (autochthonous) neoantigens were targeted with adoptively transferred TCR-engineered autologous T cells (TCR-therapy). Investigated were effects of TCR-engineered CD8+ T cells, TCR-engineered CD4+ T cells or a combination of both. The targeted tumors were established for at least three weeks and derived from primary autochthonous cancer cell cultures, resembling natural solid tumors and their heterogeneity as found in humans. CD8TCR-therapy was only effective against homogenous tumors and relapse was common in heterogeneous tumors, even when targeting multiple different autochthonous neoantigens. By contrast, a combination of CD8TCR-therapy with CD4TCR-therapy, each targeting an independent neoantigen, eradicated large and established solid tumors of natural heterogeneity. CD4TCR-therapy targeted a mutant neoantigen on tumor stroma while direct cancer cell recognition by CD8TCR-therapy was essential for cure. Thus, two cancer-specific TCRs can be essential and sufficient to eradicate heterogeneous solid tumors expressing unmanipulated, autochthonous neoantigens. Citation Format: Steven Wolf, Vasiliki Anastasopoulou, Kimberley Drousch, Markus Diehl, Boris Engels, Poh Yin Yew, Kazuma Kiyotani, Yusuke Nakamura, Karin Schreiber, Hans Schreiber, Matthias Leisegang. Adoptive transfer of one CD4TCR and one CD8TCR targeting autochthonous neoantigens are essential and sufficient for eradication of naturally heterogeneous solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB073.