| AVS 55th International Symposium & Exhibition | |
| BioMEMS Topical Conference | Tuesday Sessions |
| Session BM+MN+BI+BO-TuM |
| Session: | MEMS/NEMS for Biology and Medicine |
| Presenter: | M. Paulaitis, Ohio State University and Johns Hopkins University |
| Authors: | M. Paulaitis, Ohio State University and Johns Hopkins University C. Yue, Ohio State University N. Guzman, Ohio State University J. Schneck, Johns Hopkins School of Medicine M. Oelke, Johns Hopkins School of Medicine |
| Correspondent: | Click to Email |
We are developing protein microarrays for rapidly scanning and screening diverse T cell populations to characterize human adaptive 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 interaction is mediated by a small peptide (the antigen) 8-10 amino acids in length bound to the MHC, such that the amino acid sequence of the peptide antigen determines the specificity of the TCR/peptide-MHC (pMHC) interaction. Surface plasmon resonance studies of TCR/pMHC interactions have established that the overall range of binding affinities of stimulatory pMHC ligands is low relative to that for anti¬body-antigen interactions. Yet, these interactions have remarkably high specificity/sensitivity leading to T cell activa¬tion and different immune responses depending on the nature of the peptide. Individual T cells are also characterized by a unique TCR; therefore, pMHC microarrays printed with peptides having different amino acid sequences serve 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. This work is supported by the National Science Foundation (BES-0555281) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (1R21AI077097-01).