Chimeric T cell receptor-immunoglobulin molecules: function and applications

The antigen-specific receptors on T and B cells are related by sequence similarities, mechanisms for the generation of diversity, and a common protein domain structure. In contrast, the form of antigen recognition for T- and B-cell antigen receptors is entirely different. Whereas the B cell antigen receptor, i.e., membrane-bound immunoglobulin (Ig), has the potential to recognize a vast diversity of chemical determinants, the T cell antigen receptor (TCR) invariably recognizes oligomeric peptides bound to major histocompatibility complex molecules. A question is whether the variable domains of the TCR and Ig are similar in structure, and if so, can they be substituted one for the other. Recent experiments show that, in some combinations, the variable region of Ig can substitute for the variable region of a TCR, and convey, to a reactive T lymphocyte, the antigen specificity of an Ig molecule. This type of receptor engineering may have interesting applications in disease therapy.