HLA peptide length preferences control CD8(+) T cell responses

Rist, Melissa J., Theodossis, Alex, Croft, Nathan P., Neller, Michelle A., Welland, Andrew, Chen, Zhenjun, Sullivan, Lucy C., Burrows, Jacqueline M., Miles, John J., Brennan, Rebekah M., Gras, Stephanie, Khanna, Rajiv, Brooks, Andrew G., McCluskey, James, Purcell, Anthony W., Rossjohn, Jamie and Burrows, Scott R. (2013) HLA peptide length preferences control CD8(+) T cell responses. Journal of Immunology, 191 2: 561-571. doi:10.4049/jimmunol.1300292

Author Rist, Melissa J.
Theodossis, Alex
Croft, Nathan P.
Neller, Michelle A.
Welland, Andrew
Chen, Zhenjun
Sullivan, Lucy C.
Burrows, Jacqueline M.
Miles, John J.
Brennan, Rebekah M.
Gras, Stephanie
Khanna, Rajiv
Brooks, Andrew G.
McCluskey, James
Purcell, Anthony W.
Rossjohn, Jamie
Burrows, Scott R.
Title HLA peptide length preferences control CD8(+) T cell responses
Formatted title
HLA peptide length preferences control CD8+ T cell responses
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2013-07-15
Sub-type Article (original research)
DOI 10.4049/jimmunol.1300292
Volume 191
Issue 2
Start page 561
End page 571
Total pages 11
Place of publication United States
Publisher American Association of Immunologists
Collection year 2014
Language eng
Formatted abstract
Class I HLAs generally present peptides of 8–10 aa in length, although it is unclear whether peptide length preferences are affected by HLA polymorphism. In this study, we investigated the CD8+ T cell response to the BZLF1 Ag of EBV, which includes overlapping sequences of different size that nevertheless conform to the binding motif of the large and abundant HLA-B*44 supertype. Whereas HLA-B*18:01+ individuals responded strongly and exclusively to the octamer peptide 173SELEIKRY180, HLA-B*44:03+ individuals responded to the atypically large dodecamer peptide 169EECDSELEIKRY180, which encompasses the octamer peptide. Moreover, the octamer peptide bound more stably to HLA-B*18:01 than did the dodecamer peptide, whereas, conversely, HLA-B*44:03 bound only the longer peptide. Furthermore, crystal structures of these viral peptide–HLA complexes showed that the Ag-binding cleft of HLA-B*18:01 was more ideally suited to bind shorter peptides, whereas HLA-B*44:03 exhibited characteristics that favored the presentation of longer peptides. Mass spectrometric identification of > 1000 naturally presented ligands revealed that HLA-B*18:01 was more biased toward presenting shorter peptides than was HLA-B*44:03. Collectively, these data highlight a mechanism through which polymorphism within an HLA class I supertype can diversify determinant selection and immune responses by varying peptide length preferences.
Keyword Complex class-I
MHC class-I
3-Dimensional structure
HLA-B44 supertype
Antigenic peptide
Bound peptide
Viral epitope
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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