Functional mapping of the orientation for TCR recognition of an H2-Kb-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 interaction between MHC class I-bound peptide fragments and specific TCR have recently been described and highlight the importance of the CDR3 in determining peptide specificity. The results presented here show functional data for TCR recognition of the H2-Kb class-I restricted determinant derived from OVA (SIINFEKL) that are consistent with the TCR orientation defined by these crystal structures. In addition, we also found that the beta-chain CDR3 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-Kb-restricted peptide from the herpes simplex virus type 1 glycoprotein B (SSIEFARL), which shares a common alpha-chain contact with the OVA peptide. These results are discussed in terms of a common orientation for TCR-ligand interaction and the greater potential for TCR beta-chain CDR3 diversity in determining peptide side chain specificity.
Turner
S J
SJ
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Jameson
S C
SC
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D018360:Crystallography, X-Ray; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013329:Structure-Activity Relationship
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin