The ability of T cell receptors (TCR) to discriminate foreign from self-peptides presented by major histocompatibility complex (MHC) class II molecules is essential for an effective adaptive immune response. TCR recognition of self-peptides has been linked to autoimmune disease. Mutant self-peptides have been associated with tumors. Engagement of TCRs by a family of bacterial toxins know as superantigens has been responsible for toxic shock syndrome. Autoantibodies to V beta segments of T cell receptors have been isolated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The autoantibodies block TH1-mediated inflammatory autodestructive reactions and are believed to be a method by which the immune system compensates for disease (ref5). T Cell and TCR Diversity Most human T cells express the TCR alpha-beta and either CD4 or CD8 molecule (single positive, SP). A small number of T cells lack both CD4 and CD8 (double negative, DN). Increased percentages of alpha-beta DN T cells have been identified in some autoimmune and immunodeficiency disorders. Gamma-delta T cells are primarily found within the epithelium. They show less TCR diversity and recognize antigens differently than alpha-beta T cells. Subsets of gamma-delta T cells have shown antitumor and immunoregulatory activity.