Immunological Reviews最新文献

T cells physically interrogate their targets using tiny membrane protrusions called microvilli, forming junctions ~400 nm in diameter and ~ 15 nm deep, referred to as “close contacts”. These contacts, which are stabilized by the binding of the small adhesion protein CD2 to its ligand, CD58 and locally exclude large proteins such as the phosphatase CD45, are the sites of antigen recognition by the T-cell receptor (TCR) and very early signaling by T cells. With our collaborators, we have characterized the molecular structures of several of the key proteins mediating these early events: i.e., CD2 and its ligands, CD45, the αβ- and γδ-TCRs, and the accessory proteins CD28, CTLA-4, and PD-1. Here, we review our structural work and the insights it offers into the early events underpinning T-cell responsiveness that take place in the confined space of the close contact. We reflect on the crucial roles that the structural organization and dimensions of these proteins are likely to have in determining the sequence of events leading to antigen recognition at close contacts and consider the general implications of the structural work for explanations of how immune receptor signaling is initiated.

Vγ9Vδ2 T-cells are universally present in humans and represent one of the most prevalent TCR reactivities, evolutionarily conserved across diverse mammalian species. They are an innate-like subset featuring a semi-invariant TCR repertoire that drives their well-recognized reactivity to small, non-peptidic phosphoantigens (pAg). Crucially, they can distinguish between highly immunostimulatory microbially derived pAg and much less potent host-derived pAg, with the former effectively acting as a pathogen associated molecular pattern (PAMP) and the Vγ9Vδ2 TCR as a surrogate pattern recognition receptor (PRR). Ample evidence supports important Vγ9Vδ2-mediated contributions to immunity against diverse pathogenic bacteria and parasites, mediated by their potent effector and immunoregulatory functions. The molecular basis of the pAg sensing mechanism underpinning such responses has, however, remained highly mysterious. Despite this, past studies have established that pAg sensing is MHC-independent, extremely fast, exquisitely pAg-sensitive, and dependent upon target cell expression of key BTN-family molecules, notably BTN3A and BTN2A1. Here we contextualize these findings and several recent studies addressing pAg sensing. We integrate these into a single unified theory of pAg sensing interpretable from different perspectives, both intracellular and extracellular, biophysical, and topological. We prioritize critical questions to address in the context of this proposed model. Finally, we suggest the model will provide a molecular template for antigen recognition by other related γδ T-cell subsets.

R. Nocerino, L. Carucci, S. Coppola, F. Oglio, A. Masino, A. Agizza, L. Paparo, R. Berni Canani, “The journey toward disease modification in cow milk protein allergy,” Immunological Reviews 326, no. 1 (2024): 191–202, https://doi.org/10.1111/imr.13372. Epub 2024 Jul 24. PMID: 39046826.

Correction of the Acknowledgement Section

With regards to the article in the September 2024 issue of the Journal, the authors wish to correct the Acknowledgement Section due to the lack of the CUP codes related to funding. The correction to the Acknowledgement Section does not affect the results or conclusions of the article. The authors regret the lack.

We apologize for this error.

Current Version:

This review was supported by funding from the National Recovery and Resilience Plan, European Union–Next Generation EU (On Foods–Research and Innovation Network on Food and NutritionSustainability, Safety and Security—Working on Foods; codePE0000003), and from the Italian Ministry of Health-HealthOperational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the diet Mediterranean”(Mediterranean Diet for Human Health Lab “MeDiHealthLab”; code T5-AN- 07). The funders had no influence on the review. We thank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publishing facilitated by Università degli Studi di Napoli Federico II, as part of the Wiley-CRUI-CARE agreement.

Revised Version:

This review was supported by funding from the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of March 15 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU. Project code PE00000003, Concession Decree No. 1550 of October 11, 2022, adopted by the Italian Ministry of University and Research, CUP E63C22002030007, project title “ON Foods—Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods” and from the Italian Ministry of Health-Health Operational Plan Trajectory 5-Line of action “Creation of an action program for the fight against malnutrition in all its forms and for the dissemination of the principles of the Mediterranean diet” (Mediterranean Diet for Human Health Lab, “MeDiHealthLab,” code T5-AN-07, CUP E63C22002570006). The funders had no influence on the review. Wethank our patients and their parents/caregivers for their enthusiastic participation and dedication to all our studies. We thank all physicians, nurses, technicians, and staff members for their support during the studies. Open access publ

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