High-throughput protein microarrays for screening protein-protein interactions have promising applications in biotechnology, medical diagnostics, vaccine development, and the treatment of cancer, autoimmunity and infectious diseases. We are using this technology to rapidly screen diverse populations of T cells to characterize human influenza-specific immune responses. An important early molecular recognition event that triggers an immune response is the interaction of a T cell receptor (TCR) on the surface of the T cell with its complementary major histocompatibility complex (MHC) on the surface of antigen-presenting cells. This protein-protein interaction is mediated by a small peptide (the antigen) 8-10 amino acids in length that is bound to the MHC, such that the amino acid sequence of the peptide antigen determines the specificity of the TCR/peptide-MHC (pMHC) interaction. Individual T cells are also characterized by a unique TCR; therefore, microarrays printed with the MHC containing peptides with different amino acid sequences serves to distinguish T cells by their characteristic TCR/pMHC interactions. In addition, co-printing antibodies against cytokines secreted by the captured T cells enables an antigen-specific functional analysis of T cell activation across this population. We show that pMHC microarrays can selectively capture and enumerate antigen-specific T cells in diverse populations at high sensitivity, and that this information provides insights into the general principles governing early molecular recognition events in human immune responses. Results on the functional diversity of the human immune response will also be presented.