High Resolution Structures of Highly Bulged Viral Epitopes Bound to Major Histocompatibility Complex Class I Academic Article uri icon

abstract

  • Although HLA class I alleles can bind epitopes up to 14 amino acids in length, little is known about the immunogenicity or the responding T-cell repertoire against such determinants. Here, we describe an HLA-B*3508-restricted cytotoxic T lymphocyte response to a 13-mer viral epitope (LPEPLPQGQLTAY). The rigid, centrally bulged epitope generated a biased T-cell response. Only the N-terminal face of the peptide bulge was critical for recognition by the dominant clonotype SB27. The SB27 public T-cell receptor (TcR) associated slowly onto the complex between the bulged peptide and the major histocompatibility complex, suggesting significant remodeling upon engagement. The broad antigen-binding cleft of HLA-B*3508 represents a critical feature for engagement of the public TcR, as the narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs from HLA-B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly with the dominant TcR. Biased TcR usage in this cytotoxic T lymphocyte response appears to reflect a dominant role of the prominent peptide x major histocompatibility complex class I surface.

authors

  • Tynan, Fleur E
  • Borg, Natalie A
  • Miles, John J
  • Beddoe, Travis
  • El-Hassen, Diah
  • Silins, Sharon L
  • van Zuylen, Wendy JM
  • Purcell, Anthony W
  • Kjer-Nielsen, Lars
  • McCluskey, James
  • Burrows, Scott R
  • Rossjohn, Jamie

publication date

  • June 24, 2005