4.2 Review

A structurally based approach to determine HLA compatibility at the humoral immune level

期刊

HUMAN IMMUNOLOGY
卷 67, 期 11, 页码 847-862

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2006.08.001

关键词

HLAMatchmaker; HLA; epitope structure; histocompatibility; eplet

资金

  1. NIAID NIH HHS [R01 AI055933, AI-55933, R01 AI055933-03] Funding Source: Medline

向作者/读者索取更多资源

HLAMatchmaker is a structurally based matching program. Each HLA antigen is viewed as a string of epitopes represented by short sequences (triplets) involving polymorphic amino acid residues in antibody-accessible positions. HLAMatchmaker determines which triplets are different between donor and recipient, and this algorithm is clinically useful in determining HLA mismatch acceptability. Triplets provide however an incomplete description of the HLA epitope repertoire and expanded criteria must be used including longer sequences and polymorphic residues in discontinuous positions. Such criteria should consider the structural basis of antibody-antigen interactions including contact areas and binding energy, the essence of antigenicity. This report describes the development of a structurally defined HLA epitope repertoire based on stereochemical modeling of crystallized complexes of antibodies and different protein antigens. This analysis considered also data in the literature about contributions of amino acid residues to antigen-antibody binding energy. The results have led to the concept that HLA antigens like other antigenic proteins have structural epitopes consisting of 15-22 residues that constitute the binding face with alloantibody. Each structural epitope has a functional epitope of about 2-5 residues that dominate the strength and specificity of binding with antibody. The remaining residues of a structural epitope provide supplementary interactions that increase the stability of the antigen-antibody complex. Each functional epitope has one or more non-self residues and the term eplet is used to describe polymorphic HLA residues within 3.0-3.5 angstrom of a given sequence position on the molecular surface. Many eplets represent short linear sequences identical to those referred to as triplets but others have residues in discontinuous sequence positions that cluster together on the molecular surface. Serologically defined HLA determinants correspond well to eplets. The eplet version of HLAMatchmaker represents therefore a more complete repertoire of structurally defined HLA epitopes and provides a more detailed assessment of HLA compatibility.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.2
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据