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[Antigen peptide/MHC complex as an initiator of a signal for lymphocyte T activation]
1Laboratorium Immunogenetyki Zakładu Immunologii Klinicznej, Instytutu Immunologii i Terapii Doświadczalnej PAN, Wrocławiu.
T lymphocytes recognize antigens in the form of oligopeptides bound by major histocompatibility complex (MHC) molecules. This recognition is specific due to clonally distributed receptors (T cell receptors, TCRs) that are specific for a given peptide/given MHC combination. Recognition of appropriate (agonist) peptide bound to appropriate (usually self) MHC molecule results in conformational change in the TCR that is transmitted to TCR-associated CD3 gamma, delta, epsilon and zeta polypeptide chains. These chains then undergo a series of tyrosine phosphorylations which, in turn, cause transmission of the activation signal further along the intracellular signaling pathway. However, there are peptides (partial agonists or antagonists) that induce only incomplete signal transmission, leading to the expression of only some, but not the other, T cell functions, to the anergy, or to the apoptosis. All these situations might be exploited in future for specific immunotherapy of different pathologic conditions. Advantages and disadvantages of this approach are briefly discussed.
T lymphocytes recognize antigens in the form of oligopeptides bound by major histocompatibility complex (MHC) molecules. This recognition is specific due to clonally distributed receptors (T cell receptors, TCRs) that are specific for a given peptide/given MHC combination. Recognition of appropriate (agonist) peptide bound to appropriate (usually self) MHC molecule results in conformational change in the TCR that is transmitted to TCR-associated CD3 gamma, delta, epsilon and zeta polypeptide chains. These chains then undergo a series of tyrosine phosphorylations which, in turn, cause transmission of the activation signal further along the intracellular signaling pathway. However, there are peptides (partial agonists or antagonists) that induce only incomplete signal transmission, leading to the expression of only some, but not the other, T cell functions, to the anergy, or to the apoptosis. All these situations might be exploited in future for specific immunotherapy of different pathologic conditions. Advantages and disadvantages of this approach are briefly discussed.