An overview of immunoinformatics approaches and databases linking T cell receptor repertoires to their antigen specificity

Zvyagin, Ivan V.; Tsvetkov, Vasily O.; Chudakov, Dmitriy M.; Shugay, Mikhail

doi:10.1007/s00251-019-01139-4

Cited by 29 publications

(22 citation statements)

References 69 publications

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“…In this study, we performed a comparison of molecular functions of proteins preferentially presented by different HLA alleles. HLA restriction of peptide ligands shapes adaptive immune responses and is critical for protection against viruses and other pathogens, elimination of cancer cells and prevention of autoimmune diseases, moreover it directly shapes the repertoire of cognate T cells that form the backbone of adaptive immunity (1,(33)(34)(35). To investigate the effect of HLA restriction on the nature of the ligands presented to T cells, we studied peptides derived from the human proteome and predicted in silico binding for a set of HLA-I alleles having different recognition motifs.…”

Section: Discussionmentioning

confidence: 99%

HLA binding of self-peptides is biased towards proteins with specific molecular functions

Карнаухов

Paes

Woodhouse

et al. 2021

Preprint

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Human leukocyte antigen (HLA) is highly polymorphic and plays a key role in guiding adaptive immune responses by presenting foreign and self peptides to T cells. Each HLA variant selects a minor fraction of peptides that match a certain motif required for optimal interaction with the peptide-binding groove. These restriction rules define the landscape of peptides presented to T cells. Given these limitations, one might suggest that the choice of peptides presented by HLA is non-random and there is preferential presentation of an array of peptides that is optimal for distinguishing self and foreign proteins. In this study we explore these preferences with a comparative analysis of self peptides enriched and depleted in HLA ligands. We show that HLAs exhibit preferences towards presenting peptides from certain proteins while disfavoring others with specific functions, and highlight differences between various HLA genes and alleles in those preferences. We link those differences to HLA anchor residue propensities and amino acid composition of preferentially presented proteins. The set of proteins that peptides presented by a given HLA are most likely to be derived from can be used to distinguish between class I and class II HLAs and HLA alleles. Our observations can be extrapolated to explain the protective effect of certain HLA alleles in infectious diseases, and we hypothesize that they can also explain susceptibility to certain autoimmune diseases and cancers. We demonstrate that these differences lead to differential presentation of HIV, influenza virus, SARS-CoV-1 and SARS-CoV-2 proteins by various HLA alleles. Finally, we show that the reported self peptidome preferences of distinct HLA variants can be compensated by combinations of HLA-A/HLA-B and HLA-A/HLA-C alleles in frequent haplotypes.

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Section: Discussionmentioning

confidence: 99%

HLA binding of self-peptides is biased towards proteins with specific molecular functions

Карнаухов

Paes

Woodhouse

et al. 2021

Preprint

Self Cite

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“…After differentiation and development in the thymus, CD4 + T cells are distributed to the immune organs and tissues of the whole body through lymphatic and blood circulation. As an important component of the immune system, CD4 + T cells play an indispensable role in resisting foreign pathogens and mediate the development of autoimmunity (30,31). Abnormal CD4 + T-cell proliferation has been implicated in the development of various diseases including peripheral T-cell proliferative diseases/lymphomas, inflammatory/infection diseases, graft-versus-host disease and autoimmune diseases To examine CD4 + T cell activation, cells were stained with FITC-anti-CD4 plus APC-anti-CD44 or APC-anti-CD62L, and analyzed by flow cytometry (I).…”

Section: Discussionmentioning

confidence: 99%

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis

Bian

Wang

et al. 2020

Front. Immunol.

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Experimental autoimmune uveitis (EAU) is a CD4 + T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4 + T cell biology and hence ameliorates the development of CD4 + T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4 + T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4 + T cells. Instead, it significantly suppressed the proliferation of conventional CD4 + T cells both in vitro and in vivo. Mechanistic study showed that DH-treated CD4 + T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4 + T cells. Taken together, the current study indicates that DH-mediated suppression of CD4 + T cell proliferation may provide a promising therapeutic strategy for treating CD4 + T cell-mediated diseases.

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“…T cell receptor can only identify epitopes if it is presented on major histocompatibility complex, Epitopes binds in linear form to MHCs, they linked together into the binding groove of MHC class I and class II through interactions with the amino acids located in the pockets on the floor of MHC. (57, 58)…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatic design of multi epitopes peptide-based universal cancer vaccine using matrix metalloproteinase-9 protein as a target

Abdelmoneim

Mustafa

Abdelmageed

et al. 2020

Preprint

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Background: Cancer remains a major public health hazard despite the extensive research over the years on cancer diagnostic and treatment , this is mainly due to the complex pathophysiology and genetic makeup of cancer. A new approach toward cancer treatment is the use of cancer vaccine, yet the different molecular bases of cancers reduce the effectiveness of this approach. In this work we aim to use matrix metalloproteinase-9 protein (MMP9) which is essential molecule in the survival and metastasis of all type of cancer as a target for universal cancer vaccine design. Method: reference sequence of matrix metalloproteinase-9 protein was obtained from NCBI databases along with the related sequence, which is then checked for conservation using BioEdit, furthermore the B cell and T cell related peptide were analyzed using IEDB website. The best candidate peptide were then visualized using chimera software. Result: Three Peptides found to be good candidate for interactions with B cells (SLPE, RLYT, and PALPR), while ten peptides found as a good target for interactions with MHC1 (YRYGYTRVA, YGYTRVAEM, YLYRYGYTR, WRFDVKAQM, ALWSAVTPL, LLLQKQLSL, LIADKWPAL, KLFGFCPTR , MYPMYRFTE, FLIADKWPA) with world combined coverage of 94.77% . In addition, ten peptides were also found as a good candidates for interactions with MHC2 (KMLLFSGRRLWRFDV, GRGKMLLFSGRRLWR, RGKMLLFSGRRLWRF, GKMLLFSGRRLWRFD, TFTRVYSRDADIVIQ, AVIDDAFARAFALWS, FARAFALWSAVTPLT, MLLFSGRRLWRFDVK, GNQLYLFKDGKYWRF, NQLYLFKDGKYWRFS), with world combined coverage of 90.67%. CONCLUSION: 23 peptide-based vaccine was designed for use as a universal cancer vaccine which has a high world population coverage for MHC1(94.77%) and MHC2 (90.67%) related alleles. Introduction:Cancer is a chronic disease with varying degree of manifestations characterized by abnormal cell division and high mortality and morbidity rates, in addition it is considered the second leading cause of death worldwide with an estimated 8 million death annually and 18 million new case per year.(1-5) although cancer survival rate increased dramatically over the years in many countries, yet more work are needed to improve the prognosis of patients suffering from this depilating disease.(6, 7) Cancer can be either common or rare depending on the number of cases. Usually any cancer with a number of cases below 6 in 100000 annually is considered rare type.(8) All types of cancers cause common clinical symptoms including weight-loss, fatigue, pain, nausea, vomiting and constipation, etc.(9)Additional symptoms are specific to the site of malignancy.(10) Breast cancer is the most common site of cancer in women worldwide.(11) Lung cancer is the second most common cancer in both men and women while colorectal is the third most common type cancer in both sexes. (12) The classical management for cancer composed of chemotherapy, radiotherapy and surgery. Recently Immunotherapy started to shows very promising result in field of cancer management. Different type of immunotherapy are available including cytokine therapy, ...

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An overview of immunoinformatics approaches and databases linking T cell receptor repertoires to their antigen specificity

Cited by 29 publications

References 69 publications

HLA binding of self-peptides is biased towards proteins with specific molecular functions

HLA binding of self-peptides is biased towards proteins with specific molecular functions

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis

Immunoinformatic design of multi epitopes peptide-based universal cancer vaccine using matrix metalloproteinase-9 protein as a target

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