As with the attenuation of the antibody associations, each of the associations between HLA and IL-10 depicted inTable 5also diminished when the DPB1*0401 homozygotes were removed from the analysis. following rubella virus stimulation. Keywords:HLA Antigens, Homozygote, Rubella Virus, Measles-Mumps-Rubella Vaccine, Immunity == Introduction == The Human Leukocyte Antigen (HLA) class I and class II molecules present immunogenic epitopes to CD4+and CD8+T lymphocytes. The genes encoding the HLA molecules are extremely polymorphic with each allele capable of presenting slightly different peptide repertoires, that are determined by the molecular structure of the peptide binding domains. According to the heterozygote advantage theory, homozygosity at HLA genes should predict poor immune response to vaccines like rubella. Genetic variation within these HLA loci can have profound effects on an individuals susceptibility to infection, autoimmune disorders, or response to vaccines[14]. Similarly, homozygosity within HLA could restrict the hosts ability to present a wider repertoire of immunogenic peptides and result in diminished or ineffective cellular immunity as a result of missing epitope presentation. For example, homozygosity at HLA class I loci is associated with more rapid HIV progression [57], impaired CD4+T cell recovery after antiretroviral therapy [8], increased risk of HIV transmission to the fetus in pregnant women [9], and severe bacterial infections in sickle cell anemia patients [10,11] Likewise, heterozygosity at HLA class II loci is associated with protection against persistent disease Fertirelin Acetate after hepatitis B virus (HBV) infection [12], and may confer resistance to infection with hepatitis C virus (HCV)[13]. Rubella infections and congenital rubella syndrome (CRS) are rare in the United States but remain major health concerns in developing countries [14] and worldwide travel combined with poor adherence to vaccine recommendations results in continued exposures across the world[15]. In addition, the current two dose vaccination schedule of Measles, Mumps and Rubella vaccine (MMR) results in seroconversion rates to rubella over 95%, but a significant minority of individuals do not seroconvert or develop suboptimal Benserazide HCl (Serazide) antibody levels after vaccination[1622]. Our laboratory has previously studied the role of genetic polymorphisms including HLA haplotypes and HLA homozygosity in immune responses to vaccines containing live viruses such as measles, mumps and rubella. We have previously reported that several HLA class II alleles are associated with variations Benserazide HCl (Serazide) in rubella-specific antibody levels as well as lymphoproliferative responses to rubella[23]. Additionally, individuals homozygous at either the HLA-A or HLA-DQA1 loci were more likely to be seronegative following measles vaccination[24]. Interestingly, two doses of MMR appear to overcome this homozygote disadvantage[25]. We also found that, following Benserazide HCl (Serazide) two doses of measles vaccine, HLA class II homozygosity was associated with increased IFN secretion[26]. Our objective for this study was to examine the effect of HLA homozygosity on immune responses to rubella virus after two doses of the MMR vaccine. == Materials and Methods == == Subjects == The subjects for this study were recruited from Olmsted County, Minnesota where vaccination rates are high and there have been no cases of natural rubella infection in the community during the lifetime of the participants. The current study population came from two cohorts (stratified, random samples) of healthy children and young Benserazide HCl (Serazide) adults (1119 years old) enrolled in private or public school in Olmsted County. 342 healthy children were enrolled between December 2001 and August 2002, while an additional 396 children were recruited between Dec 2006 August 2007. The Mayo Clinic Institutional Review Board approved the study, and we obtained parental permission and subject assent (and for those 18 to 19 years of age) informed consent prior to enrollment. We reviewed the medical record of each participant for documentation of receipt of two age-appropriate doses of M-M-R II (MEASLES, MUMPS, and RUBELLA VIRUS VACCINE LIVE) (Merck and Co., Inc, West Point, PA). We also determined that each participant was in good health at the time of enrollment. Once enrolled, Benserazide HCl (Serazide) we obtained a single blood sample from each of the 738 study participants. == Rubella IgG enzyme immunoassay == For each subject, serum aliquots were stored at 80 C until use. The samples were thawed and virus-specific rubella IgG levels were determined using an automated paramagnetic particle, chemiluminescent immunoassay (Beckman Coulter, Fullerton, CA) according to the manufacturers protocol. The assays were performed using a UniCel DxI 800.
As with the attenuation of the antibody associations, each of the associations between HLA and IL-10 depicted inTable 5also diminished when the DPB1*0401 homozygotes were removed from the analysis