Infoscience

Journal article

CD8+ Cytotoxic T Lymphocyte Activation by Soluble Major Histocompatibility Complex-Peptide Dimers

CD8+ cytotoxic T lymphocyte (CTL) can recognize and kill target cells that express only a few cognate major histocompatibility complex class I-peptide (pMHC) complexes. To better understand the mol. basis of this sensitive recognition process, the authors studied dimeric pMHC complexes contg. linkers of different lengths. Although dimers contg. short (10-30-.ANG.) linkers efficiently bound to and triggered intracellular calcium mobilization and phosphorylation in cloned CTL, dimers contg. long linkers (>=80 .ANG.) did not. Based on this and on fluorescence resonance energy transfer expts., the authors describe a dimeric binding mode in which two T cell receptors engage in an anti-parallel fashion two pMHC complexes facing each other with their const. domains. This binding mode allows integration of diverse low affinity interactions, which increases the overall binding and, hence, the sensitivity of antigen recognition. In proof of this, the authors demonstrated that pMHC dimers contg. one agonist and one null ligand efficiently activate CTL, corroborating the importance of endogenous pMHC complexes in antigen recognition. [on SciFinder (R)]

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