Journal article

Genetic Bias, Diversity Indices, Physiochemical Properties and CDR3 Motifs Divide Auto-Reactive from Allo-Reactive T-Cell Repertoires

Oscar L Haigh, Emma J Grant, Thi HO Nguyen, Katherine Kedzierska, Matt A Field, John J Miles

International Journal of Molecular Sciences | MDPI | Published : 2021

Abstract

The distinct properties of allo-reactive T-cell repertoires are not well understood. To investigate whether auto-reactive and allo-reactive T-cell repertoires encoded distinct properties, we used dextramer enumeration, enrichment, single-cell T-cell receptor (TCR) sequencing and multiparameter analysis. We found auto-reactive and allo-reactive T-cells differed in mean ex vivo frequency which was antigen dependent. Allo-reactive T-cells showed clear differences in TCR architecture, with enriched usage of specific T-cell receptor variable (TRBJ) genes and broader use of T-cell receptor variable joining (TRBJ) genes. Auto-reactive T-cell repertoires exhibited complementary determining regions t..

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Grants

Awarded by Prostate Cancer Foundation Australia (PCFA)


Awarded by National and Medical Research Council of Australia (NHMRC) C.J Martin Fellowship


Awarded by Australian Research Council DECRA Fellowship


Awarded by NHMRC


Awarded by National and Medical Research Council of Australia (NHMRC)


Awarded by CDF Level 1 NHMRC Fellowship


Awarded by CDF Level 2 NHMRC Fellowship


Funding Acknowledgements

This project was supported by the Prostate Cancer Foundation Australia (PCFA) Research Grant (NCG 3913). E.J.G. was supported by a National and Medical Research Council of Australia (NHMRC) C.J Martin Fellowship (1110429) and an Australian Research Council DECRA Fellowship (DE210101479), K.K. is supported by an NHMRC Leadership Investigator Grant (1173871), M.A.F. is supported by National and Medical Research Council of Australia (NHMRC) fellowship (5121190) and J.J.M. was supported by CDF Level 1 & 2 NHMRC Fellowships (1031652 & 1131732).