Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A.

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 Immunol

journal_title

International immunology

authors

Markiewicz MA,Fallarino F,Ashikari A,Gajewski TF

doi

10.1093/intimm/13.5.625

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

625-32

issue

5

eissn

0953-8178

issn

1460-2377

journal_volume

13

pub_type

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