Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1

The enormous diversity of the T cell pool makes it difficult to determine w hether inherent biases in the naive TCR repertoire can influence T cell res ponsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immu nodominant HSV-1 determinant (gB) is characterized by a prominent bias in V P element usage, associated with a conserved and preferentially D element-e ncoded CDR3 sequence. Comparison of naive and gB-specific T cell population s revealed a similar enrichment of germline D element-encoded CDR3 sequence s in the preimmune repertoire. Strikingly, eliminating the germline coding of the gs-specific CDR3 sequence caused an almost complete loss of the domi nant subset of gB-specific T cells, illustrating that CDR3 biases can signi ficantly alter both the composition and strength of an immune response.