Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains

Abstract

The characterization of the human T-cell receptor (TCR) repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we analyzed the diversity and complexity of both the TCRα and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene) usage in ~2% of the productive human TCRβ CDR3 sequences.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-014-0060-1) contains supplementary material, which is available to authorized users.

Comparative analysis of CDR3 regions in paired human αβ CD8 T cells

“…1A) and in addition, the usage of TRBJ 2-7 and TRBJ2-1 is not random (Fig. These observations were consistent with previous large data sets which only analyzed either alpha or beta chains, suggesting that usage and distribution of TRBV and TRAV in our dataset is consistent with other sets [17,19,26,27]. These observations were consistent with previous large data sets which only analyzed either alpha or beta chains, suggesting that usage and distribution of TRBV and TRAV in our dataset is consistent with other sets [17,19,26,27].…”

“…On average, each of the four unrelated donors with a similar age yielded 194 (AE34.8) unique paired sequences from CD8+ T cells. 1A) were not detected, which is consistent with results from previous studies [17][18][19]. Among all Va segments, V7, V8-7, V9-1, V18, V34, and V40 were not detected in our sample (Fig.…”

“…1A), and among the Vb segments, V5-3, V5-7, V6-3, V6-8, V6-9, V7-1, V7-4, V7-7, and V17 ( Fig. 1A) were not detected, which is consistent with results from previous studies [17][18][19]. We next analyzed the distribution of TRAV-TRBV pairing in our dataset, and we found the frequency of each specific TRAV-TRBV combinational usage varied between 0.18 and 2.37%, as shown in Fig.…”

Conserved Vδ1 Binding Geometry in a Setting of Locus-Disparate pHLA Recognition by δ/αβ T Cell Receptors (TCRs): Insight into Recognition of HIV Peptides by TCRs

“…Because these genes can be used by both ␣␤ and ␥␦ T cells, they are termed V␣ genes when rearranged with J␣-C␣, whereas they are termed as V␦ genes when rearranged with D␦-J␦-C␦ (7). In fact, most ␥␦ T cells use the V␦1, V␦2, and V␦3 genes (5), and although these three V␦ genes do not have alternate V␣ genes, previous studies revealed that V␦1 and V␦3 can also be rearranged with J␣-C␣ genes to form a functional V␦-J␣-C␣ TCR chain that can pair with a functional TCR␤ chain (8)(9)(10)(11). Recently, one pioneering study showed that ␣␤TCRs using a V␦1 gene segment (termed ␦/␣␤TCR) can be readily found in most humans and possess the specificity for both peptide-and lipid-based Ags presented by MHC class I molecules or CD1d, respectively (12), reflecting greater levels of diversity and functional potential in the T cell lineage.…”

The somatically generated T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

“…The impact of positive selection on the TCR repertoire of mature T cells cannot be understood by sequencing only the expressed TCR or TCR chains. This is because others and we have found a fairly high percentage of individual TCR or TCR sequences are expressed in animals regardless of their MHC haplotype (Robins et al, 2010, Warren et al, 2011, Liu et al, 2014 ( Supplementary Table 1). Presumably this is at least in part possible because each individual chain is paired with a different partner(s) in animals with different MHC alleles.…”