HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection

Tomer Hertz, Christine M. Oshansky, Philippa L. Roddam, John P. DeVincenzo, Miguela A. Caniza, Nebojsa Jojic, Simon Mallal, Elizabeth Phillips, Ian James, M. Elizabeth Halloran, Paul G. Thomas, Lawrence Corey

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term targeting efficiency, and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured fromperipheral blood mononuclear cells obtained from a household cohort study performed during the 2009-2010 influenza season.We found that HLA targeting efficiency scores significantly correlated with IFN-? enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A 24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza casesmight advance clinical practices for severe H1N1 infections among genetically susceptible populations.

Original languageEnglish
Pages (from-to)13492-13497
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number33
DOIs
StatePublished - 13 Aug 2013
Externally publishedYes

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