Abstract
In this study, we demonstrated that NH2‐terminal Ser and Ile residues of pRL1b (SI‐pRL1a) (SIIPGLPLSL) are not involved in the recognition by RL♂1‐specific cytotoxic T lymphocyte. The sensitization activity observed with pRL1b (SI‐pRL1a) was not greater than that of peptides substituted with irrelevant amino acids at these positions. In serum‐free medium, pRL1a retained sensitization activity, but pRL1b (SI‐pRL1a) did not. Furthermore, addition of bestatin to serumcontaining medium blocked sensitization by pRL1b (SI‐pRL1a). On the other hand, the addition of captopril enhanced it, probably by inhibiting the degradation of pRL1a by ACE. pRL1a‐D peptide with D‐Ile in place of the L‐Ile residue of pRL1a (IPGLPLSL) showed sensitization, but SI‐pRL1a‐2,3D peptide, which has D‐Iles in place of the L‐Ile residues of pRL1b (SI‐pRL1a), and which was not cleaved between the two D‐Iles, did not. The findings suggest that pRL1a is the antigenic peptide bound to Ld molecules and pRL1b (SI‐pRL1a) peptide is its natural precursor, which generates pRL1a via proteolysis.
Keywords: BALB/c leukemia RL♂l, Cytotoxic T lymphocyte, Tumor rejection antigen peptide, Natural precursor peptide, Protease
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REFERENCES
- 1. ) Boon , T. , Cerottini , J.‐C. , van den Eynde , B. , van der Bruggen , P. and van Pel , A.Tumor antigens recognized by T lymphocytes . Annu. Rev. Immunol. , 12 , 337 – 365 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Townsend , A. and Bodmer , H.Antigen recognition by class I‐restricted T lymphocytes . Annu. Rev. Immunol. , 7 , 601 – 624 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Uenaka , A. , Ono , T. , Akisawa , T. , Wada , H. , Yasuda , T. and Nakayama , E.Identification of a unique antigen peptide pRL1 on BALB/c RL1 leukemia recognized by cytotoxic T lymphocytes and its relation to the akt oncogene . J. Exp. Med. , 180 , 1599 – 1607 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. ) Bellacosa , A. , Testa , J. R. , Staal , S. P. and Tsichlis , P. N.A retroviral oncogene, akt, encoding a serine‐threonine kinase containing an SH2‐like region . Science , 254 , 274 – 277 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Bellacosa , A. , Franke , T. F. , Gonzalez‐Portal , M. E. , Datta , K. , Taguchi , T. , Gardner , J. , Cheng , J. Q. , Testa , J. R. and Tsichlis , P. N.Structure, expression, and chromosomal mapping of c‐aktakt: relationship to v‐akt and its implications . Oncogene , 8 , 745 – 754 ( 1993. ). [PubMed] [Google Scholar]
- 6. ) Wada , H. , Matsuo , M. , Uenaka , A. , Shimbara , N. , Shimizu , K. and Nakayama , E.Rejection antigen peptides on BALB/c RLl leukemia recognized by cytotoxic T lymphocytes: deviation from the normally untranslated 5′0 region of the c‐akt proto‐oncogene activated by long terminal repeat . Cancer Res. , 55 , 4780 – 4783 ( 1995. ). [PubMed] [Google Scholar]
- 7. ) Uyttenhove , C. , van Snick , J. and Boon , T.Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. I. Rejection by syngeneic mice . J. Exp. Med. , 152 , 1175 – 1183 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Falo , L. D.Jr. , Colarusso , L. J. , Benacerraf , B. and Rock , K. L.Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules . Proc. Natl. Acad. Sci. USA , 89 , 8347 – 8350 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Kozlowski , S. , Corr , M. , Takeshita , T. , Boyd , L. F. , Pendleton , C. D. , Germain , R. N. , Berzofsky , J. A. and Margulies , D. H.Serum angiotensin‐1 converting enzyme activity processes a human immunodeficiency virus 1 gp l60 peptide for presentation by major histocompatibility complex class I molecules . J. Exp. Med. , 175 , 1417 – 1422 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Sherman , L. A. , Burke , T. A. and Biggs , J. A.Extracellular processing of peptide antigens that bind class I major histocompatibility molecules . J. Exp. Med. , 175 , 1221 – 1226 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Kozlowski , S. , Corr , M. , Shirai , M. , Boyd , L. F. , Pendleton , C. D. , Berzofsky , J. A. and Margulies , D. H.Multiple pathways are involved in the extracellular processing of MHC class I‐restricted peptides . J. Immunol. , 151 , 4033 – 4044 ( 1993. ). [PubMed] [Google Scholar]
- 12. ) Eisenlohr , L. C. , Bacik , I. , Bennink , J. R. , Bernstein , K. and Yewdell , J. W.Expression of a membrane protease enhances presentation of endogeneous antigens to MHC class‐I restricted T lymphocytes . Cell , 71 , 963 – 972 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Udaka , K. , Tsomides , T. J. and Eisen , H. N.A naturally occurring peptide recognized by alloreactive CD8+ cytotoxic T lymphocytes in association with a class I MHC protein . Cell , 69 , 989 – 998 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Udaka , K. , Tsomides , T. J. , Walden , P. , Fukusen , N. and Eisen , H. N.A ubiquitous protein is the source of naturally occurring peptides that are recognized by a CD8+ T‐cell clone . Proc. Natl Acad. Sci. USA , 90 , 11272 – 11276 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Androlewicz , M. J. and Cresswell , P.Human transporters associated with antigen processing possess a promiscuous peptide‐binding site . Immunity , 1 , 7 – 14 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Momburg , F. , Neefjes , J. J. and Hämmerling , G. J.Peptide selection by MHC‐encoded TAP transporters . Curr. Opin. Immunol. , 6 , 32 – 37 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Schumacher , T. N. M. , Kantesaria , D. V. , Heemels , M.‐T. , Ashton‐Rickardt , P. G. , Shepherd , J. C. , Fruh , K. , Yang , Y. , Peterson , P. A. , Tonegawa , S. and Pleogh , H. L.Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator . J. Exp. Med. , 179 , 533 – 540 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Rötzschke , O. , Falk , K. , Deres , K. , Schild , H. , Norda , M. , Metzger , J. , Jung , G. and Rammensee , H.‐G.Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells . Nature , 348 , 252 – 254 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Roelse , J. , Gromme , M. , Momburg , F. , Hämmerling , G. and Neefjes , J.Trimming of TAP‐translocated peptides in the endoplasmic reticulum and in the cytosol during recycling . J. Exp. Med. , 180 , 1591 – 1597 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. ) Monaco , J. J.A molecular model of MHC class‐I‐restricted antigen processing . Immunol. Today , 13 , 173 – 179 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Neefjes , J. J. and Momburg , F.Cell biology of antigen presentation . Curr. Opin. Immunol. , 5 , 27 – 34 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Momburg , F. , Roelse , J. , Hs̈mmerling , G. J. and Neefjes , J. J.Peptide size selection by the major histocompatibility complex‐encoded peptide transporter . J. Exp. Med. , 179 , 1613 – 1623 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. ) Engelhard , V. H.Structure of peptides associated with MHC class I molecules . Curr. Opin. Immunol. , 6 , 13 – 23 ( 1994. ). [DOI] [PubMed] [Google Scholar]