The T cell receptor (TCR) complex and its associated molecules are essential for T cell ontogeny and proper function of mature T cells. Deficiency in one of these components may result in major T cell deficiency or dysfunction. The clinical presentation of these defects varies widely, depending upon the severity of the genotypic abnormality. All of these immunodeficiencies are rare.
A brief review of TCR biology is first presented in this topic review to better understand disorders of the TCR complex that are associated with immunodeficiency. Detailed discussions of these topics are presented separately. Immunodeficiencies that result from defects in individual TCR complex components are then reviewed. Idiopathic cluster of differentiation 4 (CD4) lymphopenia is discussed separately. (See "The adaptive cellular immune response" and "T cell receptor genetics" and "Normal B and T lymphocyte development" and "Antigen presenting cells" and "Major histocompatibility complex (MHC) structure and function" and "Human leukocyte antigens (HLA): A roadmap" and "Idiopathic CD4+ lymphocytopenia".)
OVERVIEW OF T CELL RECEPTOR BIOLOGY
The T cell receptor (TCR) is a heterodimer, with approximately 95 percent of peripheral blood T cells possessing an alpha and a beta chain (TCR alpha-beta or TCR2) and the remainder a gamma and a delta chain (TCR gamma-delta or TCR1) (figure 1) . TCR gamma-delta is more abundant in skin and intraepithelial lymphocytes. (See "T cell receptor genetics".)
TCR chains belong structurally to the immunoglobulin gene superfamily. Thus, TCR genes undergo recombination of the variable, diversity and joining segments, called V(D)J recombination. This event is dependent upon the function of recombinase-activating genes 1 and 2 (RAG1 and RAG2) [1,2]. (See "T cell receptor genetics", section on 'T cell receptor gene organization'.)
A protein must first be processed by antigen-presenting cells (APCs) for T cells to recognize a specific antigen. APCs degrade the target antigen into several peptides. These peptides are subsequently presented on the cell surface in the groove formed by either a class I or II major histocompatibility complex (MHC) molecule. The human leukocyte antigen (HLA) system is synonymous with the human MHC. (See "Antigen presenting cells" and "Major histocompatibility complex (MHC) structure and function" and "Human leukocyte antigens (HLA): A roadmap".)