IDENTIFICATION AND CHARACTERIZATION OF MEASLES VIRUS HLA CLASS II-RESTRICTED PEPTIDES

This project is a collaboration with Dr. Gregory Poland and the Vaccine Research Group

As measles remains a significant public health concern, the World Health Organization and the National Institutes of Health have determined that the need to understand the immunogenetics of vaccine response should be a priority. In our ongoing studies, we have demonstrated significant associations between measles vaccine-induced antibody levels and specific class I and class II HLA alleles. We are now conducting a series of experiments designed to understand, at the HLA-peptide interaction level, the molecular immunogenetic mechanisms that affect immune responsiveness to immunization.

Our broad goal is to identify the unique spectrum of measles virus antigenic peptides bound by class II HLA-DRB1 molecules associated with measles vaccine low- and hyper-response and, in turn, to demonstrate that differences in this spectrum of unique measles vaccine-derived peptides presented by specific HLA molecules are associated with differences in humoral and cell-mediated immune responses. Our work is centered around the major biologic concept that the ability to respond to a vaccine antigen is predominantly determined by the genetic polymorphism of HLA genes.

Because each HLA allele binds a distinct set of naturally processed and presented peptides, our project specifically focuses on using a biochemical approach to identify the distinct spectrum of peptides bound in the HLA peptide binding groove of low- and hyper-antibody responders after receiving measles vaccine and determining the immunologic relevance of these peptides. An enchanced understanding of the interaction of peptide HLA molecules in producing cellular and humoral immune responses will result, allowing molecular design strategies for vaccines against human pathogens.