Stringent V beta requirement for the development of NK1.1(+) T cell receptor-alpha/beta(+) cells in mouse liver

The liver of C57BL/6 mice contains a major subset of CD4(+)8(-) and CD4(-)8(-) T cell receptor (TCR)-alpha/beta(+) cells expressing the polymorphic natural killer NK1.1 surface marker. Liver NK1.1(+)TCR-alpha/beta(+) (NK1(+) T) cells require interaction with beta(2)-microglobulin-associated, major histocompatibility complex class I-like molecules on hematopoietic cells for their development and have a TCR repertoire that is highly skewed to V beta 8.2, V beta 7, and V beta 2. We show here that congenic C57BL/6.V beta(a) mice, which lack V beta 8-expressing T cells owing to a genomic deletion at the V beta locus, maintain normal levels of liver NK1(+) T cells owing to a dramatic increase in the proportion of cells expressing V beta 7 and V beta 2 (but not other V beta s). Moreover, in C57BL/6 congenic TCR-V beta 3 and -V beta 8.1 transgenic mice (which in theory should not express other V beta, owing to allelic exclusion at the TCR-beta locus), endogenous TCR-V beta 8.2, V beta 7, and V beta 2 (but not other V beta s) are frequently expressed on liver NK1(+)T cells but absent on lymph node T cells. Finally, when endogenous V beta expression is prevented in TCR-V beta 3 and V beta 8.1 transgenic mice (by introduction of a null allele at the C beta locus), the development of liver NK1(+)T cells is totally abrogated. Collectively, our data indicate that liver NK1(+)T cells have a stringent requirement for expression of TCR-V beta 8.2, V beta 7, or V beta 2 for their development.