HLA targeting efficiency correlates with human T-cell responses magnitude and with mortality from Influenza-A infection (105.30)

Abstract

Abstract Experimental and computational evidence suggests that human leukocyte antigens (HLAs) preferentially bind conserved regions of viral proteins, a concept we term “targeting efficiency,” and that this preference can provide improved clearance of infection in several viral systems. One potential advantage of targeting conserved regions of a virus is the higher likelihood of cross-reactive protection from other viral strains, including those newly introduced, such as pH1N1. We hypothesized that individuals that targeted less conserved regions of influenza- A viruses would have weaker T-cell responses following infection with pH1N1. To test this hypothesis, T cell responses to A/H1N1 (2009) were measured from PBMCs obtained from a household cohort study performed during the 2009-2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFNγ ELISpot 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). Interestingly, these are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. The computational tools utilized 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.