Depression of T-cell epitope generation by stabilizing hen lysozyme

Takanori So, Hiro O. Ito, Toshitaka Koga, Sanae Watanabe, Tadashi Ueda, Taiji Imoto

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Abstract

Conformational stability of proteins is an important factor that determines their resistance/susceptibility to proteolytic digestion. Intracellular proteolysis is the key step in antigen presentation events for protein antigens; hence, it is likely that increasing protein stability reduces the antigenicity of proteins. We prepared three hen egg white lysozyme derivatives possessing different stabilities by chemical modification to clarify the relationship between conformational stability and the antigenicity of the protein. One of the derivatives was conformationally unstabilized by removing one intramolecular disulfide bond, whereas the two others were stabilized by the addition of an intramolecular crosslink. The antigenicity of these derivatives was evaluated using hen egg white lysozyme- specific T-cell hybridoma cells and a B-lymphoma cell line, A20, as antigen- presenting cells. With an increase in conformational stability, the T-cell response decreased. However, the reduction was not derived from the inefficiency of internalization to A20 cells nor the alteration of antigenicity by chemical modifications. Moreover, from analyses of their susceptibility to proteolysis and the kinetics of presentation of the T-cell epitope, it was confirmed that increasing protein stability led to the depression of T-cell epitope generation by increasing resistance to proteolysis. These results have an important implication in devising a new strategy for manipulating T-cell response by the stability of protein antigen.

Original languageEnglish
Pages (from-to)32136-32140
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number51
DOIs
Publication statusPublished - Dec 19 1997

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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