作者
Marianne JB van Stipdonk, Daniel Badia-Martinez, Marjolein Sluijter, Rienk Offringa, Thorbald van Hall, Adnane Achour
发表日期
2009/10/1
期刊
Cancer research
卷号
69
期号
19
页码范围
7784-7792
出版商
American Association for Cancer Research
简介
Immunogenicity of tumor-associated antigens (TAA) is often weak because many TAA are autoantigens for which the T-cell repertoire is sculpted by tolerance mechanisms. Substitutions at main anchor positions to increase the complementarity between the peptide and the MHC class I (MHC-I) binding cleft constitute a common procedure to improve binding capacity and immunogenicity of TAA. However, such alterations are tailored for each MHC-I allele and may recruit different CTL specificities through conformational changes in the targeted peptides. Comparative analysis of substituted melanoma-differentiation antigen gp100 in complex with H-2Db revealed that combined introduction of glycine and proline residues at the nonanchor positions 2 and 3, respectively, resulted in an agonistic altered peptide with dramatically enhanced binding affinity, stability, and immunogenicity of this TAA. Peptide …
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MJB van Stipdonk, D Badia-Martinez, M Sluijter… - Cancer research, 2009