Unraveling the chicken T cell repertoire with enhanced genome annotation.

Autor:	Früh SP; Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, Munich, Germany.; Institute of Virology, Freie Universität Berlin, Berlin, Germany., Früh MA; Independent Researcher, Munich, Germany., Kaufer BB; Institute of Virology, Freie Universität Berlin, Berlin, Germany., Göbel TW; Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, Munich, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Mar 14; Vol. 15, pp. 1359169. Date of Electronic Publication: 2024 Mar 14 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1359169
Abstrakt:	T cell receptor (TCR) repertoire sequencing has emerged as a powerful tool for understanding the diversity and functionality of T cells within the host immune system. Yet, the chicken TCR repertoire remains poorly understood due to incomplete genome annotation of the TCR loci, despite the importance of chickens in agriculture and as an immunological model. Here, we addressed this critical issue by employing 5' rapid amplification of complementary DNA ends (5'RACE) TCR repertoire sequencing with molecular barcoding of complementary DNA (cDNA) molecules. Simultaneously, we enhanced the genome annotation of TCR Variable (V), Diversity (D, only present in β and δ loci) and Joining (J) genes in the chicken genome. To enhance the efficiency of TCR annotations, we developed VJ-gene-finder , an algorithm designed to extract VJ gene candidates from deoxyribonucleic acid (DNA) sequences. Using this tool, we achieved a comprehensive annotation of all known chicken TCR loci, including the α/δ locus on chromosome 27. Evolutionary analysis revealed that each locus evolved separately by duplication of long homology units. To define the baseline TCR diversity in healthy chickens and to demonstrate the feasibility of the approach, we characterized the splenic α/β/γ/δ TCR repertoire. Analysis of the repertoires revealed preferential usage of specific V and J combinations in all chains, while the overall features were characteristic of unbiased repertoires. We observed moderate levels of shared complementarity-determining region 3 (CDR3) clonotypes among individual birds within the α and γ chain repertoires, including the most frequently occurring clonotypes. However, the β and δ repertoires were predominantly unique to each bird. Taken together, our TCR repertoire analysis allowed us to decipher the composition, diversity, and functionality of T cells in chickens. This work not only represents a significant step towards understanding avian T cell biology, but will also shed light on host-pathogen interactions, vaccine development, and the evolutionary history of avian immunology. 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 © 2024 Früh, Früh, Kaufer and Göbel.)
Databáze:	MEDLINE
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