Major sites for the differentiation of Vα14+ NKT cells inferred from the V-J junctional sequences of the invariant T-cell receptor α chain

Abstract

CD1d-restricted mouse NK1.1+ TCαβ+ natural killer T (NKT) cells predominantly use an invariant TCR α chain encoded by Vα14 and Jα281 gene segments with a one-nucleotide N region. We found that NKT cells generated in the culture of fetal liver precursors possessed Vα 14-Jα281 junctions that could be produced without the action of terminal deoxyribonucleotidyl transferase (TdT), indicating that NKT cells derived from fetal liver precursors are distinguishable from those from adult precursors with TdT expression. In fact, the frequency of the fetal-form sequences decreased with ageing. Surprisingly, the fetal-type sequences were predominantly observed in the lymphoid organs of athymic mice with the exception of bone marrow, where a sequence peculiar to the organ, with TdT-involved conversion from the invariant junction, was frequently present. These findings suggest that there are two independent sites of Vα14+ NKT cell development, the hematopoietic organs throughout life (the developing liver and adult bone marrow) and, principally, the mature thymus.