Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

T cell receptor analysis as a useful tool to understand the pathogenesis of type 1 diabetes (#19)

Maki Nakayama 1
  1. University of Colorado Denver, Aurora, CO, United States
T cell receptor (TCR) sequences are a critical component of tri-molecular complex determining tissue specificity of autoimmune diseases.  Recent improvement of sequencing technology now allows us to expand our understanding of T cell immunity contributing to the development of type 1 diabetes (T1D).  In this presentation, we will discuss several applications that can be achieved by TCR sequencing.  First, TCR sequences are an inherent signature for individual T cells, and thus are able to be used to trace how T cells infiltrate and expand between and within organs.  Identical TCR sequences are detected in different portions of pancreas as well as in peripheral immune organs including the spleen and pancreatic lymph nodes of same individuals.  This finding leads us to the second application that TCR sequences may be able to be used as biomarker if those associated with disease status are present and are quantitatively detectable in peripheral blood.   While individual patients have extremely different TCR repertoires in the pancreas, TCR sequences shared between individuals, called “public” sequences, still exist.  Sequencing of TCRs having a particular Vgene (TRAV13-1), which is considered to be preferentially used by TCRs targeting an insulin peptide presented by a DQ8 molecule, successfully identified “public” sequences detected only in the peripheral blood of newly-onset T1D patients but not in non-diabetic siblings nor in long-term T1D patients.  Thirdly, identification of TCRs enables us to discover targeted antigens.  TCR alpha and beta chain sequence pairs responding to an insulin A chain peptide have been found from the pancreas of a patient having T1D.  Lastly, TCR Vgene but not Jgene sequences encoded in germline may be a critical determinant of antigen specificity and possibly of disease susceptibility for individuals having specific HLA alleles.  Thus, TCR Vgenes may be a potential target for immunotherapy to cure and prevent T1D.