Role of the T cell receptor alpha chain in the development and phenotype of naturally arising CD4⁺CD25⁺ T cells

The T cell receptor alpha chain repertoire and the possible influence of the alpha chain on the development and phenotype of naturally arising mouse CD4⁺CD25⁺ T cells have not been extensively analysed. We used all available Vα-specific monoclonal antibodies and a sensitive multiplex genomic DNA PCR assay to study the Vα repertoire of CD4 ⁺CD25⁺ T cells in normal mice. To address whether CD4 ⁺CD25⁺ T cells express two TCR alpha chains, we have carried out four-colour flow cytometry using combinations of the available anti-Vα reagents in mice where one allele of the TCRA locus had been inactivated. Results indicate that the Vα repertoire of CD4 ⁺CD25⁺ T cells is as diverse as their CD25^- partners. In addition, CD4⁺CD25⁺ T cells develop normally in Tcrα^+/- mice and we show for the first time that despite expressing only one TCRα chain, they retain their characteristic CD4 ^low, CD3^low, TCRβ^low, CD5^high, CD45RB^low and cytoplasmic CD152^high phenotype.