TY - JOUR
T1 - HLA class II alleles and measles virus-specific cytokine immune response following two doses of measles vaccine
AU - Ovsyannikova, Inna G.
AU - Jacobson, Robert M.
AU - Ryan, Jenna E.
AU - Vierkant, Robert A.
AU - Pankratz, V. Shane
AU - Jacobsen, Steven J.
AU - Poland, Gregory A.
N1 - Funding Information:
Acknowledgements This work was supported by NIH grants AI 33144 and AI 48793. All experiments described in this manuscript comply with the current laws of the United States of America. We thank the parents and children who participated in this study. We acknowledge the efforts of the fellows, research technologists and nurses from the Mayo Vaccine Research Group. We thank Tina Agostini and Dennis Devitt for performing HLA typing. We thank Kim Zabel for her editorial assistance in preparing this manuscript.
PY - 2005/2
Y1 - 2005/2
N2 - Measles virus-specific T cells and the production of cytokines play a critical role in the immune response following measles immunization. To understand the genetic factors that influence variation in IFN-γ and IL-4 responses following measles immunization and to provide insight into the factors influencing both cellular and humoral immunity to measles, we assessed associations between human leukocyte antigen (HLA) class II genes and measles-specific Th1 and Th2-type cytokine responses in peripheral blood lymphocytes from 339 children previously vaccinated with two doses of measles-mumps-rubella vaccine (MMR-II). Median values for measles-specific IFN-γ and IL-4 secretion levels were 40.73 and 9.71 pg/ml, respectively. The global tests suggested associations between measles-specific IFN-γ response and alleles of the DRB1 and DQB1 loci (P=0.07 and P=0.02, respectively). Specifically, DRB1*0301,*0901, and*1501 alleles were significantly associated with IFN-γ secretion. The alleles that suggested evidence of an HLA association with IL-4 secretion were DRB1*0103,*0701, and*1101. Th1 cytokine responses and DQB1 allele associations revealed that the alleles with the strongest association with IFN-γ secretion were DQB1*0201,*0303,*0402, and*0602. Specific alleles with a suggestive association with low measles-specific Th2 cytokine responses were DQB1*0202 and*0503. In addition, DPB1*0101,*0201, and*0601 alleles provided suggestive evidence of an HLA association with measles-induced IFN-γ response, while DPB1*0501 was associated with an IL-4 response. These data suggest that IFN-γ and IL-4 cytokine responses to measles may be genetically restricted in part by HLA class II genes, which in turn can restrict the cellular immune response to measles vaccine.
AB - Measles virus-specific T cells and the production of cytokines play a critical role in the immune response following measles immunization. To understand the genetic factors that influence variation in IFN-γ and IL-4 responses following measles immunization and to provide insight into the factors influencing both cellular and humoral immunity to measles, we assessed associations between human leukocyte antigen (HLA) class II genes and measles-specific Th1 and Th2-type cytokine responses in peripheral blood lymphocytes from 339 children previously vaccinated with two doses of measles-mumps-rubella vaccine (MMR-II). Median values for measles-specific IFN-γ and IL-4 secretion levels were 40.73 and 9.71 pg/ml, respectively. The global tests suggested associations between measles-specific IFN-γ response and alleles of the DRB1 and DQB1 loci (P=0.07 and P=0.02, respectively). Specifically, DRB1*0301,*0901, and*1501 alleles were significantly associated with IFN-γ secretion. The alleles that suggested evidence of an HLA association with IL-4 secretion were DRB1*0103,*0701, and*1101. Th1 cytokine responses and DQB1 allele associations revealed that the alleles with the strongest association with IFN-γ secretion were DQB1*0201,*0303,*0402, and*0602. Specific alleles with a suggestive association with low measles-specific Th2 cytokine responses were DQB1*0202 and*0503. In addition, DPB1*0101,*0201, and*0601 alleles provided suggestive evidence of an HLA association with measles-induced IFN-γ response, while DPB1*0501 was associated with an IL-4 response. These data suggest that IFN-γ and IL-4 cytokine responses to measles may be genetically restricted in part by HLA class II genes, which in turn can restrict the cellular immune response to measles vaccine.
KW - ELISA
KW - HLA class II alleles
KW - IFN-γ and IL-4 cytokines
KW - Measles virus vaccine
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U2 - 10.1007/s00251-004-0756-0
DO - 10.1007/s00251-004-0756-0
M3 - Article
C2 - 15712014
AN - SCOPUS:17144367728
VL - 56
SP - 798
EP - 807
JO - Immunogenetics
JF - Immunogenetics
SN - 0093-7711
IS - 11
ER -