Conserved Residues in TCR CDR Loops and Their Role in Influencing Antigen Recognition

Abstract

The Adaptive Immune System is the body's way of identifying and destroying foreign pathogens. This process involves a recognition event utilizing two major proteins: a T cell receptor (TCR) and a Major Histocompatibility Complex (MHC) protein presenting a peptide. The complete mechanism by which a TCR recognizes an antigen (peptide‐ MHC) and proceeds to initiate the signaling cascade to destroy infected cells is still unknown. Much of our work aims to better understand the properties that might influence how a T cell receptor recognizes a peptide‐MHC. One area of interest is the role of conserved TCR residues and how this might influence TCR behavior. Preliminary bioinformatics work has shown that over 80% of TCRs have a conserved histidine residue in the CDR1β loop. Structural observation revealed that the histidine is contacting a surprisingly conserved serine or threonine residue in the CDR3β loop. To explore potential roles this interaction might have, two complementary approaches will be used to examine the effects of this interaction within T cell receptor CDR loops. Surface plasmon resonance will be used for the assessment of non‐additivity between remote CDR loops and fluorescence anisotropy will be used to detect changes in CDR loop flexibility.