Partial activation of human T cells by peptide analogs on live APC: induction of clonal anergy associated with protein tyrosine dephosphorylation.
T-cell clonal anergy induced by peptide analogs in the presence of live APC in murine systems was reported to be associated with incomplete tyrosine phosphorylation of the CD3 zeta chain followed by a lack of subsequent ZAP-70 recruitment. Furthermore, protein tyrosine phosphatase SHP-1 was associated with ZAP-70 upon T-cell activation, leading to a dominant negative signaling. In this study, we used nonself BCGa-specific human ThO clones and investigated the antagonistic/partial agonistic activities of one-residue-substituted analog peptides. The results showed that (a) certain one-residue-substituted analogs can partially activate T cells to produce lymphokines, without proliferation; (b) a peptide with a conservative one-residue substitution can induce T-cell anergy in the presence of live APC, but T cells are capable of responding to exogenously added IL-2; and (c) the induction of anergy is accompanied by marked dephosphorylation of a 110-kDa protein, without either upregulation of CD25 or any changes in CD3 zeta phosphorylation patterns, suggesting that TCR-mediated dominant negative signaling through phosphatase(s) in another mechanism that may lead to the induction of T-cell clonal anergy by altered TCR ligands.
Matsushita
S
S
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Nishimura
Y
Y
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D010455:Peptides / Q000819:agonists / Q000138:chemical synthesis / Q000276:immunology*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism*
D007376:Interleukin-2; D008222:Lymphokines; D010455:Peptides; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases