Next Generation Sequencing of the Pig ?? TCR Repertoire Identifies the Porcine Invariant NKT Cell Receptor.

ABSTRACT: Swine represent the only livestock with an established invariant NKT (iNKT) cell-CD1d system. In this study, we exploited the fact that pig iNKT cells can be purified using a mouse CD1d tetramer reagent to establish their TCR repertoire by next generation sequencing. CD1d tetramer-positive pig cells predominantly expressed an invariant V?-J? rearrangement, without nontemplate nucleotide diversity, homologous to the V?24-J?18 and V?14-J?18 rearrangements of human and murine iNKT cells. The coexpressed ?-chain used a V? segment homologous to the semivariant V?11 and V?8.2 segments of human and murine iNKT cell receptors. Molecular modeling found that contacts within CD1d and CDR1? that underlie fine specificity differences between mouse and human iNKT cells are conserved between pigs and humans, indicating that the response of porcine and human iNKT cells to CD1d-restricted Ags may be similar. Accordingly, pigs, which are an important species for diverse fields of biomedical research, may be useful for developing human-based iNKT cell therapies for cancer, infectious diseases, and other disorders. Our study also sequenced the expressed TCR repertoire of conventional porcine ?? T cells, which identified 48 V?, 50 J?, 18 V?, and 18 J? sequences, most of which correspond to human gene segments. These findings provide information on the ?? TCR usage of pigs, which is understudied and deserves further attention.

SUBMITTER: Yang G 

PROVIDER: S-EPMC6606045 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature