NOVEL METHODS FOR MHC TETRAMER LIBRARY TECHNOLOGY

Abstract

The ability to examine the status of T cells offers insights to the immune response against a disease and contributes to the formulation of effective therapies or vaccines. MHC tetramers have been widely used for quantification and phenotypic characterization of T cell responses in basic and clinical research. This thesis describes novel concepts involving the MHC tetramer library technology. First, we report the successful implementation of a chemical technology that enables the high-throughput generation of recombinant MHC tetramer library through a reductively-induced peptide-exchange method. This includes the conceptualization, design, synthesis and validation of a novel collection of chemolabile ligands for human and murine MHCs. Second, we describe a novel finding on degeneracy in peptide presentation of the immunodominant Influenza A virus M158-66 epitope by alleles from two HLA loci. The structural basis behind this degenerate presentation and its possible implication on the molecular recognition of CTLs will also be elucidated.