Virus infection expands a biased subset of T cells that bind tetrameric class I peptide complexes

We have used a TCR β-chain transgenic mouse to examine the relationship between the ability of a T cell to bind soluble class I-peptide complexes and its response to antigenic stimulation in vivo. T cells from gBT-I.3β TCR β-chain transgenic mice preferentially carried TCR α-chains bearing the same Vα2 V region as found in the parent receptor specific for an immunodominant HSV-1 gB-peptide. Furthermore, CD8⁺ T cells from these mice bound K^b- gB tetrameric complexes with relatively high frequency, and most of these cells contained a Vα2 TCR α-chain. Detailed sequence analysis of the tetramer-binding peripheral T cells showed that this was a heterogenous population expressing TCR with only partial sequence similarity to the parent receptor, which took the form of preferential inclusion of the parental Jα 16 element. Infection with HSV-1, however, selected a subset of tetramer-positive T cells. This was based on the emergence of a co-dominant Jα usage and selection of a restricted CDR3α length. Therefore, the ability to bind soluble MHC-peptide complexes does not always correlate with the ability of a T cell to respond to its cognate antigen after in vivo stimulation.