A Simplified Amino Acidic Alphabet to Unveil the T-Cells Receptors Antigens: A Computational Perspective.

Autor:	Iannuzzi R; Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi', Milan, Italy., Rossetti G; Molecular Oncology and Immunology, FIRC Institute of Molecular Oncology (IFOM), Milan, Italy., Spitaleri A; Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy., Bonnal RJP; Molecular Oncology and Immunology, FIRC Institute of Molecular Oncology (IFOM), Milan, Italy., Pagani M; Molecular Oncology and Immunology, FIRC Institute of Molecular Oncology (IFOM), Milan, Italy.; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy., Mollica L; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in chemistry [Front Chem] 2021 Feb 25; Vol. 9, pp. 598802. Date of Electronic Publication: 2021 Feb 25 (Print Publication: 2021).
DOI:	10.3389/fchem.2021.598802
Abstrakt:	The exposure to pathogens triggers the activation of adaptive immune responses through antigens bound to surface receptors of antigen presenting cells (APCs). T cell receptors (TCR) are responsible for initiating the immune response through their physical direct interaction with antigen-bound receptors on the APCs surface. The study of T cell interactions with antigens is considered of crucial importance for the comprehension of the role of immune responses in cancer growth and for the subsequent design of immunomodulating anticancer drugs. RNA sequencing experiments performed on T cells represented a major breakthrough for this branch of experimental molecular biology. Apart from the gene expression levels, the hypervariable CDR3α/β sequences of the TCR loops can now be easily determined and modelled in the three dimensions, being the portions of TCR mainly responsible for the interaction with APC receptors. The most direct experimental method for the investigation of antigens would be based on peptide libraries, but their huge combinatorial nature, size, cost, and the difficulty of experimental fine tuning makes this approach complicated time consuming, and costly. We have implemented in silico methodology with the aim of moving from CDR3α/β sequences to a library of potentially antigenic peptides that can be used in immunologically oriented experiments to study T cells' reactivity. To reduce the size of the library, we have verified the reproducibility of experimental benchmarks using the permutation of only six residues that can be considered representative of all ensembles of 20 natural amino acids. Such a simplified alphabet is able to correctly find the poses and chemical nature of original antigens within a small subset of ligands of potential interest. The newly generated library would have the advantage of leading to potentially antigenic ligands that would contribute to a better understanding of the chemical nature of TCR-antigen interactions. This step is crucial in the design of immunomodulators targeted towards T-cells response as well as in understanding the first principles of an immune response in several diseases, from cancer to autoimmune disorders. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Iannuzzi, Rossetti, Spitaleri, Bonnal, Pagani and Mollica.)
Databáze:	MEDLINE
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