AN INVARIANT T-CELL RECEPTOR-ALPHA CHAIN IS USED BY A UNIQUE SUBSET OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-SPECIFIC CD4-8- T-CELLS IN MICE AND HUMANS( AND CD4)

The mouse thymus contains a mature T cell subset that is distinguishab le from the mainstream thymocytes by several characteristics. It is re stricted in its usage of T cell receptor (TCR) VP genes to V(beta)8, V (beta)7, and V(beta)2. Its surface phenotype is that of activated/memo ry cells. It carries the natural killer NK1.1 surface marker. Furtherm ore, though it consists entirely of CD4(+) and CD4(-)8(-) cells, its s election in the thymus depends solely upon major histocompatibility co mplex (MHC) class I expression by cells of hematopoietic origin. Force d persistence of CD8, in fact, imparts negative selection. Here, we ha ve studied the TCR repertoire of this subset and found that, whereas t he beta chain V-D-J junctions are quite variable, a single invariant c t chain V(alpha)14-J281 is used by a majority of the TCRs. This surpri singly restricted usage of the V(alpha)14-J281 a! chain is dependent o n MHC class I expression, but independent of the MHC haplotype. In hum ans, a similar unusual population including CD4(-)8(-) cells can also be found that uses a strikingly homologous, invariant alpha chain V(al pha)24-JQ. Thus, this unique V-alpha-J(alpha) combination has been con served in both species, conferring specificity to some shared nonpolym orphic MHC class I/peptide self-ligand(s). This implies that the T cel l subset that it defines has a specialized and important role, perhaps related to its unique ability to secrete a large set of lymphokines i ncluding interleukin 4, upon primary stimulation in vitro and in vivo.