Mechanisms of T cell receptor antagonism: implications in the treatment of disease

Current Molecular Medicine
B N Dittel

Abstract

The adaptive immune response is often required for the successful clearing of infectious pathogens. Antigen presenting cells (APC) present peptide antigens derived from pathogens to T cells via major histocompatibility complex (MHC) molecules. T cells then become activated and differentiate into effector cells with the capacity to kill infected cells or to induce an anti-pathogen antibody response. In autoimmunity, this T cell response is directed against self-antigens and often leads to deleterious effects on specific tissues. Likewise, T cell responses to allogeneic MHC molecules in transplants also leads to pathology. By introducing subtle changes in the antigenic peptide amino acid content, T cell activation can be inhibited, thereby preventing T cell effector functions. This strategy of TCR antagonism has been used successfully in vitro and in vivo to inhibit models of autoimmunity and allorecognition. In addition, a variety of pathogens that often result in chronic disease following infection, also have seemingly evolved natural mechanisms to inhibit T cell responses by antagonism. These microorganisms express natural variants of certain proteins, that when presented to T cells have the capacity to specifically inhibit T ...Continue Reading

Citations

Jan 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Leandro J CarreñoAlexis M Kalergis
Nov 24, 2004·The Journal of Experimental Medicine·Dipica HaribhaiCalvin B Williams
Oct 22, 2013·Journal of Proteomics·Raúl Manzano-RománManuel Fuentes

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