Abstract:
:Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can also be processed and presented by class I MHC molecules has suggested that epitope spreading could occur for CD8(+) cytotoxic T lymphocyte (CTL) responses as well. In the context of anti-tumor immunity, expansion of a CTL response to include secondary epitopes could improve the efficacy of therapeutic vaccines. To determine directly whether epitope spreading can occur during an anti-tumor immune response, two defined class I MHC-binding peptides in the P815 tumor model were utilized. We observed that immunization against the single tumor peptide, P1A, followed by rejection of a P1A(+) tumor, subsequently yielded CTL activity and tumor protection against a P1A(-) tumor variant. P1A immunized mice that subsequently rejected tumor challenge developed CTL against a second defined epitope, P1E. These results indicate that, as for class II-restricted peptides in autoimmune disease, epitope spreading can occur for class I-restricted peptides during tumor rejection. A broadened CTL response may help eliminate outgrowth of antigen-negative tumor variants.
journal_name
Int Immunoljournal_title
International immunologyauthors
Markiewicz MA,Fallarino F,Ashikari A,Gajewski TFdoi
10.1093/intimm/13.5.625subject
Has Abstractpub_date
2001-05-01 00:00:00pages
625-32issue
5eissn
0953-8178issn
1460-2377journal_volume
13pub_type
杂志文章abstract::NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing beta cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice i...
journal_title:International immunology
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更新日期:2000-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-02-01 00:00:00
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更新日期:1996-06-01 00:00:00
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更新日期:2002-07-01 00:00:00
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更新日期:1999-03-01 00:00:00
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doi:10.1093/intimm/11.7.1075
更新日期:1999-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-02-01 00:00:00
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更新日期:2003-04-01 00:00:00
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更新日期:1997-08-01 00:00:00
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