FUNCTIONAL MAPPING OF THE ORIENTATION FOR TCR RECOGNITION OF AN H2-K-B-RESTRICTED OVALBUMIN PEPTIDE SUGGESTS THAT THE BETA-CHAIN SUBUNIT CAN DOMINATE THE DETERMINATION OF PEPTIDE SIDE-CHAIN SPECIFICITY

T cells recognize a complex of antigenic peptide bound to the class I or class II products of the MHC, Crystallographic analysis of the inte raction between MHC class I-bound peptide fragments and specific TCR h ave recently been described and highlight the importance of the CDR3 i n determining peptide specificity, The results presented here show fun ctional data for TCR recognition of the H2-K-b class-I restricted dete rminant derived from OVA (SIINFEKL) that are consistent with the TCR o rientation defined by these crystal structures, In addition, we also f ound that the beta-chain CDRB dominates side chain specificity for the most exposed regions within this peptide, The data also suggest that this orientation and pattern of beta-chain dominance may extend to the recognition of a second H2-K-b-restricted peptide from the herpes sim plex virus type 1 glycoprotein B (SSIEFARL), which shares a common cy- chain contact with the OVA peptide, These results are discussed in ter ms of a common orientation for TCR-ligand interaction and the greater potential for TCR beta-chain CDR3 diversity in determining peptide sid e chain specificity.