Selection of variable-joining region combinations in the α chain of the T cell receptor

Most T lymphocytes express an antigen-specific receptor composed of two subunits, α and β, each of which can exhibit structural variability. A complex selection process operates on T cells during development in the thymus such that cells expressing only particular αβ-receptors migrate to the periphery. The α-chain repertoire was dissected at different stages of the selection process by using the polymerase chain reaction (PCR) technique to amplify only those transcripts of a particular variable region gene (V ₅₈). Sequences from these V₅₈ cDNAs reveal the predominant expression of four joining (J) segments by T cells in the adult thymus, suggesting that molecular or cellular processes select particular V _αJ_α combinations during development. T cells expressing one of these V₅₈J_α chains appear to have been negatively selected at a later stage, since these transcripts were present in the spleen at approximately one-tenth the level in the thymus. Results also indicate that residues present at the V_αJ_α junction may be important in an early selection process.