TCR Analyses: T-cell receptor CDR3 analysis: Molecular fingerprinting of the T-cell receptor repertoire

Maeurer, Markus J.

T-cells play a crucial role in immune surveillance against transformed cells and intracellular infections; they are involved in auto-immune reactions. They recognize their targets, i.e. MHC / peptide complexes, trough the T-cell receptor. TCR usage determines the molecular interaction of the immune system with biologically relevant MHC/peptide molecules. The TCR coding genes (variable, diversity and junctional) determine the molecular composition of the TCR alpha and beta heterodimer. The random association of the VDJ genes constitutes the complementarity determining region 3 (CDR3) responsible for antigen recognition and TCR specificity. The molecular composition of a T-cell population can be objectively defined by measuring the CDR3 region. Qualitative and quantitative comparisons of the TCR composition in different anatomic compartments, or longitudinally over time, allow to asses the entire TCR repertoire. This methodology can be supplemented with functional T-cell based assays and aids to objectively describe any alteration in the T-cell pool. TCR CDR3 analysis is useful in immunomonitoring, e.g. examining patients after BMT or solid organ transplantation, patients with HAART therapy, or patients receiving molecularly defined vaccines.