๐ Novel immunodominant peptide presentation strategy: A featured HLA-A*2402-restricted cytotoxic T-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein
Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of in vitro studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and ฮฒ2-microglobulin (ฮฒ2m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides. Copyright ยฉ 2010, American Society for Microbiology.
keywords
๐ severe acute (1373)
๐ syndrome coronavirus (1074)
๐ respiratory syndrome (2004)
๐ acute respiratory (1734)
๐ crystal structure (114)
author
๐ค Liu, Jun
๐ค Wu, Peng
๐ค Gao, Feng
๐ค Qi, Jianxun
๐ค Kawana-Tachikawa, Ai
๐ค Xie, Jing
๐ค Vavricka, Christopher J.
๐ค Iwamoto, Aikichi
๐ค Li, Taisheng
๐ค Gao, George F.
year
โฐ 2010
journal
๐ Journal of Virology
issn
๐ 0022538X 10985514
volume
84
number
22
page
11849-11857
citedbycount
29
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