Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 281, Issue 43, Pages 32676-32683Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M604847200
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Funding
- NCI NIH HHS [CA 101542] Funding Source: Medline
- NIAID NIH HHS [AI 48120] Funding Source: Medline
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A hallmark of the immune system is the ability to ignore self-antigens. In attempts to bypass normal immune tolerance, a post-translational protein modification was introduced into self-antigens to break T and B cell tolerance. We demonstrate that immune tolerance is bypassed by immunization with a post-translationally modified melanoma antigen. In particular, the conversion of an aspartic acid to an isoaspartic acid within the melanoma antigen tyrosinase-related protein (TRP)-2 peptide-(181-188) makes the otherwise immunologically ignored TRP-2 antigen immunogenic. Tetramer analysis of isoAsp TRP-2 peptide- immunized mice demonstrated that CD8(+) T cells not only recognized the isoaspartyl TRP-2 peptide but also the native TRP-2 peptide. These CD8(+) T cells functioned as cytotoxic T lymphocytes, as they effectively lysed TRP-2 peptide-pulsed targets both in vitro and in vivo. Potentially, post-translational protein modification can be utilized to trigger strong immune responses to either tumor proteins or potentially weakly immunogenic pathogens.
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