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Discrepancy in CD3‐Transmembrane Peptide Activity between In Vitro and In Vivo T‐Cell Inhibition
Author(s) -
Collier S.,
Bolte A.,
Manolios N.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01806.x
Subject(s) - in vivo , in vitro , transmembrane protein , peptide , microbiology and biotechnology , chemistry , cd3 , biology , biochemistry , immunology , genetics , antigen , cd8 , receptor
Electrostatic amino acid interactions between receptor subunits within the T‐cell antigen receptor (TCR) transmembrane domain are critical for the formation of the TCR‐CD3 complex. Core peptide, a short peptide corresponding to the TCR‐ α transmembrane region, containing two positively charged amino acids, is known to inhibit T‐cell function in vitro and in vivo . The aim of this study was to examine peptides corresponding to the syntactic transmembrane CD3 region binding to TCR‐ α for their ability to inhibit T‐cell activation in vitro and in vivo . Three peptides matching the transmembrane sequence of CD3‐ δ , ‐ ɛ and ‐ γ were synthesized and tested in different biological in vitro and in vivo systems for their effect on T‐cell activity. The CD3‐peptides had no impact on T‐cell function in vitro , but surprisingly, decreased signs of inflammation in the adjuvant arthritis rat model in vivo . Preliminary evidence suggests that peptides with CD3 transmembrane‐derived sequences can inhibit an immune response as assessed by adjuvant‐induced arthritis. The lack of in vitro activity may lead to a wasteful disregard of active compounds in the process of drug discovery and development.