Modulation of peptide specific T cell responses by non-native flanking regions

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• 作者：Wilkinson ; Katalin A. ; Vordermeier ; Martin H. ; Kajtá ; r ; Judit ; Jurcevic ; Stipo ; Wilkinson ; Robert ; et. al.
• 关键词：CD4⁺ T-cell epitope ; flanking regions ; synthetic antigens ; antigenic determinant ; solution conformation ; synthetic peptides ; 38 kDa protein of M. tuberculosis
• 刊名：Molecular Immunology
• 出版年：1997
• 出版时间：December, 1997
• 年：1997
• 卷：34
• 期：18
• 页码：1237-1246
• 全文大小：924 K

文摘

The deduced core (⁷⁵RYPNVTI⁸¹) from a T-cell stimulatory epitope of the 38 kDa protein of M. tuberculosis was studied to identify the structural elements required for the creation of a synthetic peptide antigen from an epitope core, which alone was not capable of inducing CD4⁺ T-cell responses. Peptides were prepared with extensions composed of native and/or non-native sequences to clarify the role of the flanking regions adjacent to the epitope core. Their binding to isolated H-2-A^b MHC glycoprotein as well as T-cell stimulatory capacity were assayed using a specific murine hybridoma T-cell line [38.H6], lymph node cells from the native 20-mer peptide primed C57BL/10 mice and human PBMCs from sensitised individuals. Elongation of the epitope core by four alanines at both N- and C-terminals resulted in a 15-mer peptide A₄-75-81-A₄ which was stimulatory for hybridoma T-cells and showed a small decrease in H-2-A^b binding. Substitution of one Ala by Ser in the N-terminal flank had pronounced effect and peptide A₂SA-75-81-A₄ proved to be more effective than the native 20-mer sequence in the hybridoma as well as in the LN cell proliferation assays. The binding of this peptide and that of the native one were similar.