Hapten addition to an MHC class I-binding peptide causes substantial adjustments of the TCR structure of the responding CD8(+) T cells

T cell responses against hapten-modified peptides play an important role in the pathogenesis of certain diseases, including contact dermatitis and all ergy. However, the structural features of TCRs recognizing bulky, potential ly mobile hapten groups remain poorly defined. To analyze the structural ba sis of TCR recognition of defined hapten-modified peptides, the immunodomin ant octapeptide derived from vesicular stomatitis virus nucleoprotein (VSV8 ) was modified with a trinitrophenyl (TNP) group at the primary TCR contact residues (position 4 or 6) and used for immunization of mice carrying eith er the TCR alpha- or beta -chain of a VSV8 (unmodified)/H-2K(b)-Specific CT L clone as a transgene. Such mice allow independent analysis of one TCR cha in by maintaining the other fixed. The TCR V gene usage of the responding T cell population was specifically altered depending upon the presence of th e TNP group and its position on the peptide. The CDR3 sequences of the TNP- modified peptide-specific TCRs showed a preferential J region usage in both the CDR3 alpha and beta loops, indicating that the J regions of both CDR3s are critical for recognition of TNP-modified peptides. In contrast to our previous observations showing the prime importance of CDR3 beta residues en coded by D-segment or N-addition nucleotides for recognition of position 6 of unmodified VSV8, our studies of TNP-modified peptides demonstrate the im portance of the J beta region, while the Ja region was crucial for recogniz ing both TNP-modified and unmodified peptides. These data suggest that diff erent structural strategies are utilized by the CDR3 alpha and beta loops t o allow interaction with a haptenated peptide.