Secretion of a chimeric T-cell receptor-immunoglobulin protein

To produce sufficient quantities of soluble T-cell receptor protein for detailed biochemical and biophysical analyses we have explored the use of immunoglobulin-T-cell receptor gene fusions. In this report we describe a chimeric gene construct containing a T-cell receptor α-chain variable (V) domain and the constant (C) region coding sequences of an immunoglobulin γ2a molecule. Cells transfected with the chimeric gene synthesize a stable protein product that expresses immunoglobulin and T-cell receptor antigenic determinants as well as protein A binding sites. We show that the determinant recognized by the anticlonotypic antibody A2B4.2 resides on the V(α) domain of the T-cell receptor. The chimeric protein associates with a normal λ light chain to form an apparently normal tetrameric (H₂L₂, where H = heavy and L = light) immunoglobulin molecule that is secreted. Also of potential significance is the fact that a T-cell receptor V(β) gene in the same construct is neither assembled nor secreted with the λ light chain, and when expressed with a C(κ) region it does not assemble with the chimeric V(α)C(γ₂a) protein mentioned above. This indicates that not all T-cell receptor V regions are similar enough to immunoglobulin V regions for them to be completely interchangeable.