TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines.
TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines.
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DOI：
10.1007/s00262-012-1217-5
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发表时间：
2012-10
影响因子：
5.8
通讯作者：
Slansky, Jill E.
中科院分区：
文献类型：
--
作者：
Jordan, Kimberly R.;Buhrman, Jonathan D.;Sprague, Jonathan;Moore, Brandon L.;Gao, Dexiang;Kappler, John W.;Slansky, Jill E.
A major goal of immunotherapy for cancer is the activation of T cell responses against tumor-associated antigens (TAAs). One important strategy for improving antitumor immunity is vaccination with peptide variants of TAAs. Understanding the mechanisms underlying the expansion of T cells that respond to the native tumor antigen is an important step in developing effective peptide-variant vaccines. Using an immunogenic mouse colon cancer model, we compare the binding properties and the TCR genes expressed by T cells elicited by peptide variants that elicit variable antitumor immunity directly ex vivo. The steady-state affinity of the natural tumor antigen for the T cells responding to effective peptide vaccines was higher relative to ineffective peptides, consistent with their improved function. Ex vivo analysis showed that T cells responding to the effective peptides expressed a CDR3β motif, which was also shared by T cells responding to the natural antigen and not those responding to the less effective peptide vaccines. Importantly, these data demonstrate that peptide vaccines can expand T cells that naturally respond to tumor antigens, resulting in more effective antitumor immunity. Future immunotherapies may require similar stringent analysis of the responding T cells to select optimal peptides as vaccine candidates. The online version of this article (doi:10.1007/s00262-012-1217-5) contains supplementary material, which is available to authorized users.
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