Tetramer analysis of human autoreactive CD4-positive T cells

Self-reactivity is an intrinsic property of the human immune system. Autoreactive T cells derive directly from the developmental requirement for TCR engagement by self-antigens during lymphocyte maturation. The fundamental questions implicating these autoreactive cells in human autoimmunity then, are not "Where do they come from?", but rather "Why do they persist?", "How do they become activated?", and "How are they regulated or deleted?". New technologies, in which peptide-MHC (pMHC) ligands used for T-cell recognition are utilized as soluble fluorescent multimers, now permit the direct visualization of antigen-specific autoreactive T-lymphocytes. By using multimer technology to study self-reactive cells present in autoimmune patients and control individuals, a very broad range of autoreactive potential has been identified.