The diversity of the TCR repertoire that is integral to effective aá T-cell function is generated by somatic recombination of variable (V), diversity (D-á chains only) and joining (J) gene segments of the component a and á chains. To facilitate the development of techniques to examine bovine T-cell responses we undertook an extensive analysis of genomic and cDNA data to characterise the bovine TCRá gene repertoire. Analysis of the third bovine genome assembly demonstrates that although the TCRB locus is still incomplete, the TCRá gene repertoire in cattle is significantly larger than that of either humans or mice. Most notably, several of the Vá subfamilies, such as Vá1, 10 and 13 have undergone extensive duplication, containing 35, 16 and 40 members respectively. Much of this expansion appears to be due to duplication of 'cassettes' containing multiple genes leading to tandemly arranged duplicates incorporating members of two or more subfamilies (e.g. Vá18-Vá17-Vá2-Vá10). In all, 130 Vá genes distributed over 24 subfamilies have been identified in the genome so far. Compared to other Species examined, the bovine genome also has expanded Dá and Já gene repertoires due to triplicate rather than duplicate copies of the DJC region of the TCRB locus. The majority (126/130) of the Vá genes and all of the Dá, Já and Cá genes present in the genome assembly are located of 4 large scaffolds, 3 of which have been mapped to chromosome 4. Extensive analysis of over 900 TCRá chain sequences generated from cDNA studies completed in our laboratory have identified more than 30 Vá genes that are not present in the current bovine genome assembly, indicating that the full genomic Vá repertoire remains undefined. In contrast, comparison to cDNA and EST data suggests that the full Já repertoire is represented in the genome assembly. Combination of the cDNA and genomic analyses suggest that the functional bovine TCRá gene repertoire is composed of over 100 Vá genes, 3 Dá genes and 17 Já genes. The results of this work indicate that the bovine TCRá gene repertoire is the largest yet characterised. The dramatic expansion of membership of certain Vá subfamilies and comparison to the human and murine TCRá gene repertoires raises interesting questions concerning the forces influencing the evolution of this immunologically important locus.
- genome TCR