It is now clear that two lineages of T cells bearing the CD3 antigen can be defined, based on the nature of the heterodimeric receptor chains (o~ or~ 1~) expressed. Here, Charles Janeway and colleagues speculate that the~ 1~ receptors (TCR1) may be largely specific for class I MHC (major histocompatibility complex) antigens different from those expressed on most somatic cells. Two potential functions of TCR l-bearing cells are surveillance of epithelia and differentiation of T cells bearing~ receptors (TCR2) in the thymus.

The elusiveness of the T-cell receptor responsible for the recognition of antigen in the context of self MHC-encoded molecules has yielded to cellular and molecular immunologists. It is now well established that the genes encoding the o~ and 13 chains of these structures can account for the specificity of the cells expressing them 1.2, although the molecular details of antigen-MHC recognition are not yet understood. Furthermore, many functions of cells bearing these receptors have been well characterized. However, the pursuit of the elusive T-cell receptor revealed a gene of equal interest and unknown function, the T-cell receptor-like~, gene 3. Here, the great need is for a coherent paradigm to explain the structure of this gene and its function in the immune response. In this article, we propose an hypothesis to account for~/gene structure and expression, and suggest a function for the cells that express this gene.