The molecular rules that govern CD4+ T-helper cell recognition of peptide- MHCII. (360G-Wellcome-095767_Z_11_Z)

The molecular interactions that govern T-cell activation: T-cells recognise foreign antigens in the form of short peptides presented at the cell surface in complex with major histocompatibility complex molecules (pMHC). pMHCs are recognised by the highly variable membrane bound T-cell receptor (TCR). There are two main subsets of T-cells; CD8+ cytotoxic T lymphocytes (CTLs) that recognize pMHC class I (pMHCI) and play a key role in directly killing tumour cells and cells infected with pathogens , and CD4+ T helper cells (Th-cells) that recognize pMHC class II (pMHCII) and play a key role in orchestrating immune responses. Research Goals: 1: Use bacterially expressed soluble pMHCII molecules to investigate the structural and biophysical rules that govern CD4+ T helper cell responses. 2: Develop enhanced peptide ligands to artificially increase the affinity of the TCR/pMHCII interaction. 3: Engineer enhanced pMHCII multimers for the enumeration and isolation of CD4+ T helper cell s. 4: Establish whether modified peptide ligands, that increase the affinity of the TCR/pMHCII interaction, can be used to develop improved peptide vaccines for treating human diseases. Understanding the molecular parameters that govern CD4+ T helper cell immunity is essential for developing therapies and diagnostics for a number of important human diseases.