Systematic pattern analyses of Vδ2+ TCRs reveal that shared “public” Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status

• Published in: Frontiers in immunology Vol. 13; p. 960920
• Main Authors: Deng, Lihua, Harms, Anna, Ravens, Sarina, Prinz, Immo, Tan, Likai
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 27.09.2022
• Subjects: Immunology; TCR distance; TCR sequencing; TRD rearrangement; Vγ9Vδ2+ T cells; γδ TCR
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.960920

Background Vγ9Vδ2 + T cells are a major innate T cell subset in human peripheral blood. Their Vδ2 + VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called “public” versions of Vδ2 + TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring “public” Vγ9Vδ2 + T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent “private” clones. Methods Shared “public” Vδ2 + TCRs were identified from Vδ2 + TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2 + CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2 + TCRs. Results Vδ2 + CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2 + TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2 + TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2 + TRDJ1 TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2 + TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2 + TCRs was positively associated with expansion status. Conclusion To conclude, the heterogeneity of Vδ2 + TCRs is mainly determined by TRDJ -usage and the length of CDR3aa sequences. Public Vδ2 + TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status.