Cutting edge: MHC class II-restricted peptides containing the inflammation-associated marker 3-nitrotyrosine evade central tolerance and elicit a robust cell-mediated immune response

被引:81
作者
Birnboim, HC
Lemay, AM
Lam, DKY
Goldstein, R
Webb, JR
机构
[1] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada
[2] Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada
[3] Ottawa Hosp Res Inst, Ottawa, ON, Canada
[4] Univ Ottawa, Dept Med, Div Rheumatol, Ottawa, ON, Canada
[5] Novasante Corp, Ottawa, ON, Canada
关键词
D O I
10.4049/jimmunol.171.2.528
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Nitrotyrosine is widely recognized as a surrogate marker of up-regulated inducible NO synthase expression at sites of inflammation. However, the potential immunogenicity Of autologous proteins containing nitrotyrosine has not previously been investigated. Herein, we used the I-E-K-restricted T cell epitope of pigeon/moth cytochrome c PCC/MCC88-103) to assess the ability of T cells to recognize ligands containing nitrotyrosine. Substitution of the single tyrosine (Y97) in PCC/MCC88-103 with nitrotyrosine abrogates recognition by the MCC88-103-specific T cell hybridoma 2B4. CBA (H2(K)) mice immunized with MCC88-103 or nitrated MCC88-103 peptides produce T cell responses that are mutually exclusive. Transgenic mice that constitutively express PCC under the control of an MHC class I promoter are tolerant toward immunization with MCC88-103 but exhibited a robust immune response against nitrated MCC88-103. Analysis of T cell hybridomas specific for nitrated-MCC88-103 indicated that subtle differences in TCR VDJ gene usage are sufficient to allow nitrotyrosine-specific T cells to escape the processes of central tolerance.
引用
收藏
页码:528 / 532
页数:5
相关论文
共 37 条
  • [1] Andersen MH, 1999, J IMMUNOL, V163, P3812
  • [2] Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis
    Bäcklund, J
    Carlsen, S
    Höger, T
    Holm, B
    Fugger, L
    Kihlberg, J
    Burkhardt, H
    Holmdahl, R
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (15) : 9960 - 9965
  • [3] EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY
    BECKMANN, JS
    YE, YZ
    ANDERSON, PG
    CHEN, J
    ACCAVITTI, MA
    TARPEY, MM
    WHITE, CR
    BECKMAN, JS
    [J]. BIOLOGICAL CHEMISTRY HOPPE-SEYLER, 1994, 375 (02): : 81 - 88
  • [4] A tale of two controversies -: Defining both the role of peroxidases in nitrotyrosine formation in vivo using eosinophil peroxidase and myeloperoxidase-deficient mice, and the nature of peroxidase-generated reactive nitrogen species
    Brennan, ML
    Wu, WJ
    Fu, XM
    Shen, ZZ
    Song, W
    Frost, H
    Vadseth, C
    Narine, L
    Lenkiewicz, E
    Borchers, MT
    Lusis, AJ
    Lee, JJ
    Lee, NA
    Abu-Soud, HM
    Ischiropoulos, H
    Hazen, SL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) : 17415 - 17427
  • [5] Ceriello A, 2001, DIABETOLOGIA, V44, P834
  • [6] Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury
    Chatterjee, PK
    Patel, NSA
    Kvale, EO
    Cuzzocrea, S
    Brown, PAJ
    Stewart, KN
    Mota-Filipe, H
    Thiemermann, C
    [J]. KIDNEY INTERNATIONAL, 2002, 61 (03) : 862 - 871
  • [7] Beneficial effects of GW274150, a novel, potent and selective inhibitor of NOS activity, in a rodent model of collagen-induced arthritis
    Cuzzocrea, S
    Chatterjee, PK
    Mazzon, E
    McDonald, MC
    Dugo, L
    Di Paola, R
    Serraino, I
    Britti, D
    Caputi, AP
    Thiemermann, C
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 453 (01) : 119 - 129
  • [8] RESCUE OF T-CELL-SPECIFIC V(D)J RECOMBINATION IN SCID MICE BY DNA-DAMAGING AGENTS
    DANSKA, JS
    PFLUMIO, F
    WILLIAMS, CJ
    HUNER, O
    DICK, JE
    GUIDOS, CJ
    [J]. SCIENCE, 1994, 266 (5184) : 450 - 455
  • [9] Posttranslational protein modifications: new flavors in the menu of autoantigens
    Doyle, HA
    Mamula, MJ
    [J]. CURRENT OPINION IN RHEUMATOLOGY, 2002, 14 (03) : 244 - 249
  • [10] Post-translational protein modifications in antigen recognition and autoimmunity
    Doyle, HA
    Mamula, MJ
    [J]. TRENDS IN IMMUNOLOGY, 2001, 22 (08) : 443 - 449