Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96

Tatsuaki Ishii, Heiichiro Udono, Taketoshi Yamano, Hiroyuki Ohta, Akiko Uenaka, Toshiro Ono, Akio Hizuta, Noriaki Tanaka, Pramod K. Srivastava, Eiichi Nakayama

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Abstract

We have previously demonstrated that vaccination with heat shock proteins hsp70, hsp90, and gp96 elicits specific immunity against the tumor from which the hsps were purified. Although the association of tumor Ag peptides with these hsps have been suggested, the identification of the peptides or their precursors stripped from the hsps remained to be resolved. We show in this report that an L(d)-restricted cytotoxic T lymphocyte epitope of a mouse leukemia RL♂1 and its precursors are associated with the chaperones hsp90 and hsp70 in the cytosol and gp96 in the lumen of the endoplasmic reticulum. Hsp70 was associated with only final sized octamer, while hsp90 was found to associate with the octamer and two distinct precursor peptides. The gp96 was associated with the octamer and one of the two precursors. Thus, each of the hsps bound a distinct set of peptides. Our results have demonstrated for the first time that the hsps associate not only with final sized tumor Ag peptide but also with its precursors. The implication of this evidence is also discussed in terms of the roles of hsps in MHC class I Ag processing/presentation.

Original languageEnglish
Pages (from-to)1303-1309
Number of pages7
JournalJournal of Immunology
Volume162
Issue number3
Publication statusPublished - Feb 1 1999

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Neoplasm Antigens
Heat-Shock Proteins
Peptides
Neoplasms
T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
Endoplasmic Reticulum
Cytosol
Immunity
Leukemia
Vaccination

ASJC Scopus subject areas

  • Immunology

Cite this

Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. / Ishii, Tatsuaki; Udono, Heiichiro; Yamano, Taketoshi; Ohta, Hiroyuki; Uenaka, Akiko; Ono, Toshiro; Hizuta, Akio; Tanaka, Noriaki; Srivastava, Pramod K.; Nakayama, Eiichi.

In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1303-1309.

Research output: Contribution to journalArticle

Ishii, T, Udono, H, Yamano, T, Ohta, H, Uenaka, A, Ono, T, Hizuta, A, Tanaka, N, Srivastava, PK & Nakayama, E 1999, 'Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96', Journal of Immunology, vol. 162, no. 3, pp. 1303-1309.
Ishii, Tatsuaki ; Udono, Heiichiro ; Yamano, Taketoshi ; Ohta, Hiroyuki ; Uenaka, Akiko ; Ono, Toshiro ; Hizuta, Akio ; Tanaka, Noriaki ; Srivastava, Pramod K. ; Nakayama, Eiichi. / Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. In: Journal of Immunology. 1999 ; Vol. 162, No. 3. pp. 1303-1309.
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