Distribution and development of the postnatal murine Vδ1 T-cell receptor repertoire

Abstract

Murine γ/δ T cells express canonical Vγ5Vδ1 chains in the epidermis and Vγ6Vδ1 chains at reproductive sites. Both subsets carry an identical Vδ1-Dδ2-Jδ2 chain which completely lacks junctional diversity. These cells are thought to monitor tissue integrity via recognition of stress-induced self antigens. In this study, we showed by reverse transcription-polymerase chain reaction (RT-PCR), complementarity determining region 3 (CDR3) spectratyping and sequencing of the junctional regions of Vδ1 chains from C57BL/6 mice (aged 1 day to 14 months) that the canonical Vδ1-Dδ2-Jδ2 chain is also consistently present at other sites such as the thymus, gut, lung, liver, spleen and peripheral blood. In addition, we found multiple Vδ1 chains with fetal type rearrangements which were also shared among organs and among animals. These Vδ1 chains were typically characterized by a conserved amino acid motif, 'GGIRA'. Furthermore, by analysing the early postnatal period at days 10 and 16, we demonstrated that the diversification of the thymic Vδ1 repertoire is not paralleled by a diversification of extrathymic Vδ1+γ/δ T cells. This indicates that only fetal type rearrangements survive at extrathymic sites. In conclusion, γ/δ T cells expressing the canonical Vδ1-Dδ2-Jδ2 chain are not unique to the skin and reproductive sites. Furthermore, we found other γ/δ T cells expressing fetal type Vδ1 chains which were shared among different organs and animals. Thus, γ/δ T cells expressing conserved Vδ1 chains are likely to have important functions. We suggest a model in which this subset continuously recirculates throughout the organism and rapidly responds to stress-induced self antigens.