The goal of this research is to determine the antigen specificity of antibodies in serum samples from healthy subjects, stratified by HLA genotype. Our interest is in understanding how HLA variation shapes the autoantibody repertoire in the absence of overt disease. We utilize the Phage Immuno-Precipitation Sequencing (PhIP-Seq), comprised of 744,000 peptides tiled across the human proteome, representing the entire human peptidome for interrogation of antibody specificity. We examine serum samples from approximately 1000 healthy volunteers. To reduce confounding in the interpretation of results, we will enrich for samples homozygous at the primary HLA class II loci, HLA-DRB1 and HLA-DQB1, which are the predominant loci associated in autoimmune disease and for which ten or greater serum samples are available for the given haplotype. In this study, we expect to gain a more comprehensive understanding of the role of HLA in human immunity.