During an immune response, it is important that T-cells be able to distinguish between a person's own cells and tissues (self) and foreign and/or infected cells (non-self) as the T-cells are responsible for targeting harmful cells for destruction and for signalling B-cell lymphocytes (another type of white blood cell) to begin producing antibodies

Receptors are protein structures on the surface of T-cells that allow them to identify and evaluate self and non-self cells and other substances that can produce an immune response (antigens). There are two types of T-cell receptors, each containing two different subunits. The T-cell receptor genes control the development of these receptor subunits. Rearrangements in these genes are a normal part of T-cell development. The purpose of the rearrangements is to produce a wide variety of receptors within the T-cell population to recognise and address the vast number of antigens that a person may encounter. This means that the receptor gene rearrangements and the receptors in a normal T-cell lymphocyte population are usually very diverse (polyclonal).

With a T-cell lymphoma, an abnormal T-cell lymphocyte begins to clone itself, producing numerous identical cells. The identical, cloned (monoclonal) cells do not function normally, their replication is not regulated, and they may not die as normal cells do. A cancerous monoclonal population of T-cells accumulates, begins to crowd out normal cells, and may eventually spread throughout the lymphatic system and blood to other lymph nodes and tissue, including the bone marrow.

All of the monoclonal cells produced will have identical T-cell receptor gene rearrangement profiles. The cancerous (neoplastic) clones are generally large and therefore the clonal cells are the predominant T-cells present in affected tissue. Detection of a predominant T-cell receptor gene rearrangement profile often indicates the presence of a neoplastic T-cell population. This can help to establish the diagnosis of a T-cell lymphoma or to evaluate for residual or recurrent disease after treatment.