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Medical Microbiology

Food for Health: Publications

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Full-Text Articles in Medicine and Health Sciences

How An Alloreactive T-Cell Receptor Achieves Peptide And Mhc Specificity, Yuan Wang, Nishant K. Singh, Timothy T. Spear, Lance M. Hellman, Kurt H. Piepenbrink, Rachel H. Mcmahan, Hugo R. Rosen, Craig W. Vander Kooi, Michael I. Nishimura, Brian M. Baker May 2017

How An Alloreactive T-Cell Receptor Achieves Peptide And Mhc Specificity, Yuan Wang, Nishant K. Singh, Timothy T. Spear, Lance M. Hellman, Kurt H. Piepenbrink, Rachel H. Mcmahan, Hugo R. Rosen, Craig W. Vander Kooi, Michael I. Nishimura, Brian M. Baker

Food for Health: Publications

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2− individual …


A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker Nov 2016

A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker

Food for Health: Publications

T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a …