Fig. P1.

Investigating the requirement of the TCR CDRs for engagement with MHC class I and II molecules. (A) To diversify the germ-line CDRs, recombination signal sequences (RSS), which direct DNA rearrangement (termed recombination cassette), were inserted into TCR-β chain CDR1 or CDR2 as highlighted. For constructs (i) and (ii), the non-targeted CDR was in WT configuration, whereas construct (iii) contained artificial versions of both germ-line CDRs, with CDR1 being targeted. The modified chains were introduced into hematopoietic stem cells and transferred to recipient mice. Analysis of the target CDRs reveals a high degree of diversity. (B) Both germ-line CDRs were replaced with artificial linkers or with germ-line CDRs from a TCR-γ chain. Complete loss of germ-line CDR structure did not prevent selection of T cells. Strikingly, self- and nonself-MHC discrimination was maintained because nonself- but not self-skin grafts were rejected.