Tynan, Fleur E., Borg, Natalie A., Miles, John J., Beddoe, Travis, El-Hassen, Diah, Silins, Sharon L., van Zuylen, Wendy J.M., Purcell, Anthony W., Kjer-Nielsen, Lars, McCluskey, James, Burrows, Scott R., and Rossjohn, Jamie (2005) High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I: implications for T-cell receptor engagement and T-cell immunodominance. Journal of Biological Chemistry, 280 (25). pp. 23900-23909.

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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·major histocompatibility complex class I surface.

Item ID:	45422
Item Type:	Article (Research - C1)
ISSN:	1083-351X
Funders:	National Health and Medical Research Council (NHMRC), Australian Research Council (ARC), Juvenile Diabetes Research Foundation (JDRF), Roche Organ Transplantation Research Foundation (ROTRF), Wellcome Trust (WT)
Date Deposited:	07 Sep 2016 05:37
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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