Hb(64-76) epitope binds in different registers and lengths to I-Ek and I-Ak.
The nature of peptide binding to MHC molecules is intrinsically degenerate, in what, one given MHC molecule can accommodate numerous peptides which are structurally diverse, and one given peptide can bind to different alleles. The structure of the MHC class II molecules allows peptides to extend out of the binding groove at both ends and these residues can potentially influence the stability and persistence of peptide/class II complexes. We have previously shown that both I-E(k) and I-A(k)-restricted T cell hybridomas could be generated against the Hb(64-76) epitope. In this study, we characterized the binding register of the Hb(64-76) epitope to I-A(k), and showed that it was shifted by one residue in comparison to its binding to I-E(k), and did not use a dominant anchor residue at P1. This conclusion was further supported by the modeling of the Hb(64-76) epitope bound to I-A(k), which revealed that all of its putative anchor residues fit into their corresponding pockets. We identified the naturally processed Hb epitopes presented by both I-E(k) and I-A(k), and found that they consisted of different species. Those associated with I-A(k) being 20-22 residues long, whereas, those found to I-E(k) contained 14-16 residues. These findings suggested that the lack of a dominant P1 anchor could be compensated by the selection of longer peptides. Overall, these studies revealed the Hb(64-76) epitope bound to I-E(k) and I-A(k) in distinct registers and lengths, demonstrating the plasticity MHC molecules have in generating distinct TCR ligands from the same amino acid sequence.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
K
K
Vidal
C
C
Daniel
I
I
Vidavsky
C A
CA
Nelson
P M
PM
Allen
D017951:Antigen Presentation; D001665:Binding Sites; D001667:Binding, Competitive; D000939:Epitopes; D006454:Hemoglobins / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D008958:Models, Molecular; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding
D000939:Epitopes; D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; C024138:I-E-antigen; D010446:Peptide Fragments; D010455:Peptides; C079201:hemoglobin (64-76)