The generation and maintenance of a diverse repertoire of T cells is an important component of T cell immunity. The T cell receptor (TCR) repertoire of mature T cells is the result of complex rearrangements of the α and β TCR genes followed by selection processes resulting in approximately 25 million different TCR in health adults.
Several factors influence the TCR repertoire of each individual including negative and positive selection in the thymus, HLA type, and infections. After hematopoietic stem cell transplantation, the T cell receptor repertoire must be reconstituted. Reconstitution of the T-cell repertoire is influenced by several factors including pre-HSCT conditioning, the number of T cells in the donor graft, thymic function, infections, GVHD, immunosuppressive medications, and interactions between recipient and donor hematopoietic cells. In general, the repertoire complexity of the marrow correlates with the immune function of the recipient.
TCR diversity is created by rearrangement and fusion between exons encoding the V, D, and J segments of the gene along with insertion and deletion of nucleotides at junctional regions. TCR families can be selectively amplified using primers that are specific for each TCR gene family and diversity within the family can be evaluated by determining the length of amplicons spanning the complementary determining region 3 (CDR3) which plays an important role in defining TCR specificity.
This is a robust method with sufficient sensitivity to detect differences that are correlated with the clinical status of transplant recipients. It is generally accepted that normal, healthy individuals show a Gaussian distribution for the amount of each allowed TCR length for each TCR gene family. The distribution becomes abnormal (i.e., "oligoclonal" with one or a small number of peaks and non-Gaussian distribution, or "skewed" with several peaks but non-Gaussian distribution) under a variety of circumstances (e.g., transplant, infection, GvHD).
