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Broad-based influenza-specific CD8+ T cell response without the typical immunodominance hierarchy and its potential implication

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journal contribution
posted on 13.07.2021, 08:15 by Miaojuan Huang, Rong Xu, Cristina Triffon, N Mifsud, Weisan Chen
Syngeneic murine systems have pre-fixed MHC, making them an imperfect model for investigating the impact of MHC polymorphism on immunodominance in influenza A virus (IAV) infections. To date, there are few studies focusing on MHC allelic differences and its impact on immunodominance even though it is well documented that an individual’s HLA plays a significant role in determining immunodominance hierarchy. Here, we describe a broad-based CD8+ T cell response in a healthy individual to IAV infection rather than a typical immunodominance hierarchy. We used a systematic antigen screen approach combined with epitope prediction to study such a broad CD8+ T cell response to IAV infection. We show CD8+ T cell responses to nine IAV proteins and identify their minimal epitope sequences. These epitopes are restricted to HLA-B*44:03, HLA-A*24:02 and HLA-A*33:03 and seven out of the nine epitopes are novel (NP319–330# (known and demonstrated minimal epitope positions are subscripted; otherwise, amino acid positions are shown as normal text (for example NP 319–330 or NP 313–330)), M1124–134, M27–15, NA337–346, PB239–49, HA445–453 and NS1195–203 ). Additionally, most of these novel epitopes are highly conserved among H1N1 and H3N2 strains that circulated in Australia and other parts of the world.

Funding

This project was supported by the NHMRC program grant 567122 to WC.

History

Publication Date

01/06/2021

Journal

Viruses

Volume

13

Issue

6

Article Number

1080

Pagination

(p. 1-17)

Publisher

MDPI

ISSN

1999-4915

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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