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Immunologic significance of HLA class I genes in measles virus-specific IFN-γ and IL-4 cytokine immune responses

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Abstract

The variability of immune responses modulated by human leukocyte antigen (HLA) genes and secreted cytokines is a significant factor in the development of a protective effect of measles vaccine. We studied the association between type 1 helper T cells (Th1)- and Th2-like cytokine immune responses and HLA class I alleles among 339 schoolchildren who previously received two doses of the measles vaccine. Median values for measles-specific interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1–176.7] and 9.7 pg/ml (IQR 2.8–24.3), respectively. Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-γ secretion. HLA-A*3101 and Cw*0303 were associated with a higher median IFN-γ response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-γ response. We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion. Understanding the genetic factors that influence variations in cytokine secretion following measles vaccination will provide insight into the factors that influence both cell-mediated and humoral immunity to measles.

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Abbreviations

CTL:

Cytotoxic T lymphocyte

HLA:

human leukocyte antigen

PBMC:

peripheral blood mononuclear cells

PHA:

phytohemagglutinin

RSCA:

reference strand conformation analysis

SSP:

sequence-specific primer

IFN-γ:

interferon gamma

IL-4:

interleukin-4

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Acknowledgements

We thank the parents and children who participated in this study. We acknowledge the efforts of the fellows, nurses, and technicians from the Mayo Vaccine Research Group. We thank Carla L. Tentis for her editorial assistance in preparing this manuscript. This work was supported by NIH grants AI 48793, AI 33144, AI53592, and Mayo Clinic General Clinical Research Center Program MO1 RR00585.

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Authors and Affiliations

  1. Mayo Vaccine Research Group, Mayo Clinic College of Medicine, Guggenheim 611C, 200 First Street SW, Rochester, MN, 55905, USA

    Inna G. Ovsyannikova, Jenna E. Ryan, Robert M. Jacobson & Gregory A. Poland

  2. Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Robert A. Vierkant & V. Shane Pankratz

  3. Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Robert M. Jacobson

  4. Program in Translational Immunovirology and Biodefense, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Gregory A. Poland

Authors
  1. Inna G. Ovsyannikova
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  2. Jenna E. Ryan
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  3. Robert A. Vierkant
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  4. V. Shane Pankratz
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  5. Robert M. Jacobson
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  6. Gregory A. Poland
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Correspondence to Gregory A. Poland.

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Ovsyannikova, I.G., Ryan, J.E., Vierkant, R.A. et al. Immunologic significance of HLA class I genes in measles virus-specific IFN-γ and IL-4 cytokine immune responses. Immunogenetics 57, 828–836 (2005). https://doi.org/10.1007/s00251-005-0061-6

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  • DOI: https://doi.org/10.1007/s00251-005-0061-6

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