Extrathymic Differentiation of a T Cell Bearing Invariant Vα14Jα281 TCR

Abstract

We found that a homogenous CD4-/CD8- T cell bearing an invariant TCR encoded by Vα14Jα281 with a one-base N-region is highly dominant in the periphery (2-3% in spleen). Surprisingly, the high expression of this invariant Vα14 TCR is a general phenomenon in all laboratory strains irrespective of MHC haplotype and in some wild mouse subspecies. The majority of Vα14+ TCR is associated with Jα other than Jα281 during the neonatal stage, after which the frequency of invariant Vα14Jα281 TCR expression increases with time reaching a maximum at around 5-8 weeks after birth. The dominant expression of Vα14Jα281 TCR is found in both euthymic and athymic mice. These results indicate that homogenous Vα14Jα281 T cells are positively selected in the periphery without thymic influence and that their VJ junction is important for positive selection. We also demonstrate that Vα14⁺ TCR gene rearrangements take place at extrathymic sites, such as bone marrow, liver, and intestine, since frequent nonproductive Vα14 TCR products and Vα14-Jα281 gene mediated signal sequences in circular DNA are detected as a result of TCR rearrangements in extrathymic tissues rather than in the thymus. This indicates the extrathymic development of Vα14Jα281 T cells. Furthermore, the biological roles of homogenous T cells bearing Vα14Jα281 TCR and the human counterpart of this invariant TCR are also discussed.

Key Words:

• invariant TCR
• Va14
• extrathymic development
• signal sequence
• double negative
• autoreactive