title: Identification of cell proliferation-associated epitope on CD98 oncoprotein using phage display random peptide library.
abstract: CD98 is known as a cell surface antigen expressed in proliferating normal tissues and in almost all tumor cells. Although the function of CD98 is not yet fully elucidated, it is suggested that CD98 is concerned functionally in lymphocyte activation, cell proliferation, and malignant transformation. Monoclonal antibody against human CD98 heavy chain (h.c.), termed HBJ127, shows inhibition of lymphocyte activation and tumor cell growth in vitro. These observations suggest that the epitope recognized by HBJ127 may be crucial for CD98 function. In the present study, the authors investigated the epitope recognized by HBJ127 using a phage display random heptapeptide library. Approximately 2.4 x 10(4)-fold amplification of eluted phage titer was obtained after three rounds of panning of the phage library against HBJ127. Seven different heptapeptide sequences were isolated from 30 randomly selected clones of the post-panning phage population. A homology search using ClustalW identified the peptide sequence corresponding to (442)AFS(444) of human CD98 h.c. It was also found that (443)F is a human-specific amino acid by comparing sequences of human, rat, and mouse origin. Reduced reactivity of HBJ127 was detected against the phenylalanine-substituted peptide but not detected against the alanine or serine-substituted one. It has been identified that HBJ127 reacts only with human species and the HBJ127 epitope position is predicted in 418-529 of human CD98 h.c. From these results and observations, it was estimated that (442)AFS(444) of human CD98 h.c. may be the HBJ127 epitope. Moreover, (443)F may be critical for the binding of HBJ127 against human CD98 h.c.
authors: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. itohk@u-shizuoka-ken.ac.jp
authors: Kunihiko
authors: K
authors: Itoh
authors: Kazuyuki
authors: K
authors: Inoue
authors: Hideki
authors: H
authors: Hayashi
authors: Toshio
authors: T
authors: Suzuki
authors: Takashi
authors: T
authors: Masuko
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics*; D001435:Bacteriophages; D002455:Cell Division; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D027261:Fusion Regulatory Protein-1 / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D019151:Peptide Library
chemical_list: D015703:Antigens, CD; D004277:DNA, Single-Stranded; D000939:Epitopes; D027261:Fusion Regulatory Protein-1; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D019151:Peptide Library
references: J Mol Biol. 1995 Apr 14;247(5):932-46
references: 7536850
references: Nat Biotechnol. 2005 Sep;23(9):1105-16
references: 16151404
references: Cancer Res. 2007 Apr 15;67(8):3518-23
references: 17440057
references: J Natl Cancer Inst. 2005 Nov 16;97(22):1663-70
references: 16288119
references: J Mol Biol. 1992 Oct 5;227(3):711-8
references: 1404385
references: Gan. 1983 Dec;74(6):819-21
references: 6607858
references: Biochem Biophys Res Commun. 1999 Sep 7;262(3):720-5
references: 10471392
references: Biochemistry. 1995 Mar 28;34(12):3948-55
references: 7535098
references: J Biol Chem. 1998 Sep 11;273(37):23629-32
references: 9726963
references: Biochem J. 1995 Dec 15;312 ( Pt 3):863-70
references: 8554532
references: Oncogene. 2000 Dec 14;19(54):6209-15
references: 11175335
references: J Biochem. 1999 Jan;125(1):123-9
references: 9880807
references: Cancer Res. 1986 Mar;46(3):1478-84
references: 2417704
references: Gene. 1993 Jun 15;128(1):29-36
references: 8508957
references: Eur J Immunol. 2006 May;36(5):1267-74
references: 16568495
references: J Immunol. 1981 Apr;126(4):1409-14
references: 7204970
references: Jpn J Cancer Res. 1989 Jan;80(1):10-4
references: 2565325
references: J Immunol. 1986 Mar 15;136(6):2055-61
references: 3950410
references: Adv Immunol. 1994;57:191-280
references: 7872158
references: Science. 1985 Jun 14;228(4705):1315-7
references: 4001944
references: Annu Rev Immunol. 1994;12:433-55
references: 8011287
references: Methods Mol Biol. 2002;178:1-37
references: 11968478
references: Int Immunol. 2007 Mar;19(3):331-6
references: 17272286
references: Cell Immunol. 2006 Feb;239(2):136-43
references: 16814270
references: Jpn J Cancer Res. 1985 May;76(5):386-94
references: 3924712
references: Eur J Immunol. 1994 Nov;24(11):2868-73
references: 7525309
references: Cancer Res. 2005 Apr 15;65(8):3410-8
references: 15833876
references: J Immunol. 2004 Jul 1;173(1):394-401
references: 15210798
references: J Biol Chem. 1994 Sep 30;269(39):23853-6
references: 7929027