ABSTRACT
The fundamental basis for central tolerance is that interaction of antigen with immature clones of lymphocytes already expressing antigen receptors results in their elimination. This theory, for which Burnet and Medawar received the Nobel Prize in 1960, is now recognized to involve a mechanism that causes elimination of self-reactive lymphocytes (clonal deletion) on contact with self antigens. Immature precursor T cells derived from bone marrow stem cells migrate to the thymus to mature into immunocompetent T cells. T cells with specificity for self appear during normal development in the thymus as the result of the expression of combinations of V-segment genes (Sections D3, E3, and F3). These self-reactive T cells must be eliminated to prevent autoimmunity.
