HIVgp120 activates autoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing.

T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing T cell priming and, if they are self-maintained, may sustain autoimmune diseases. Herein, we demonstrate for the first time a mechanism by which the gp120 human immunodeficiency virus-I, by downregulating plasma membrane CD4 and increasing its processing, unveils hidden CD4 epitopes, inducing an autoimmune-specific T cell response.