Use of Microbial Microarrays to Define Antibody Specificity

The formation of alloantibodies against red blood cell (RBC) antigens is the most frequent immune barrier to blood transfusion. Among these antibodies, those that occur naturally within the first few months of life against carbohydrate-based ABO blood group antigens are the most prevalent. Individuals who lack the A or B antigen produce antibodies directed against the corresponding absent antigen. Unlike antibodies that arise following antigen exposure during pregnancy or transfusion, these spontaneously occurring antibodies suggest a role for environmental influences. Early investigations proposed that microbial pathogens bearing carbohydrate motifs resembling blood group antigens could provide such a stimulus. However, characterizing antibody specificities against diverse microbes remains difficult, as each organism often requires unique growth conditions. To address this challenge, glycan microarray technology has been developed, which has enabled high-throughput assessment of antibody binding to a wide variety of microbial carbohydrate determinants, including those mimicking blood group antigens. In this work, we highlight the use of microbial glycan microarrays for defining specificity of antibodies and lectins against microbial mimics of blood group and related antigens.