Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity.
Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity.
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DOI：
10.1084/jem.20011194
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发表时间：
2002-03-04
期刊：
影响因子：
--
通讯作者：
Wiley DC
中科院分区：
文献类型：
--
作者：
Hennecke J;Wiley DC
对甲型流感病毒血凝素（HA）抗原肽具有特异性的α/β T细胞受体（TCR）HA1.7是HLA-DR 1限制性的，但对同种主要组织相容性复合体（MHC）II类分子HLA-DR 4呈递的HA肽具有交叉反应性。我们在这里报告的HA1.7/DR 4/HA复合物的结构，确定通过X射线晶体学在2.4 μ m的分辨率。该复合物的整体结构与先前报道的HA1.7/DR 1/HA复合物的结构非常相似。DR 1和DR 4之间的氨基酸序列差异位于肽结合沟的深处，TCR无法直接接触，通过改变位置P5和P6处HA肽残基的构象，能够间接影响pMHC表面的抗原性。尽管TCR HA1.7对由DR 1和DR 4呈递的HA具有交叉反应性并且耐受这些构象差异，但其他HA特异性TCR对这些变化敏感。我们还发现依赖于MHC II类肽结合沟的宽度上的序列的结合肽通过比较HA 1.7/DR 4/HA复合物与结构的DR 4提出的胶原蛋白肽。TCR交叉反应性的结构研究强调了MHC序列差异如何通过移动肽原子间接影响TCR结合。
The α/β T cell receptor (TCR) HA1.7 specific for the hemagglutinin (HA) antigen peptide from influenza A virus is HLA-DR1 restricted but cross-reactive for the HA peptide presented by the allo-major histocompatibility complex (MHC) class II molecule HLA-DR4. We report here the structure of the HA1.7/DR4/HA complex, determined by X-ray crystallography at a resolution of 2.4 Å. The overall structure of this complex is very similar to the previously reported structure of the HA1.7/DR1/HA complex. Amino acid sequence differences between DR1 and DR4, which are located deep in the peptide binding groove and out of reach for direct contact by the TCR, are able to indirectly influence the antigenicity of the pMHC surface by changing the conformation of HA peptide residues at position P5 and P6. Although TCR HA1.7 is cross-reactive for HA presented by DR1 and DR4 and tolerates these conformational differences, other HA-specific TCRs are sensitive to these changes. We also find a dependence of the width of the MHC class II peptide-binding groove on the sequence of the bound peptide by comparing the HA1.7/DR4/HA complex with the structure of DR4 presenting a collagen peptide. This structural study of TCR cross-reactivity emphasizes how MHC sequence differences can affect TCR binding indirectly by moving peptide atoms.
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影响因子：
56.9
作者：
Fremont, DH;Hendrickson, WA;Kappler, J
通讯作者：
Kappler, J
影响因子：
15.3
作者：
Baker, BM;Turner, RV;Biddison, WE
通讯作者：
Biddison, WE
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
DOI：
10.1084/jem.181.5.1847
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammer J;Gallazzi F;Bono E;Karr RW;Guenot J;Valsasnini P;Nagy ZA;Sinigaglia F
通讯作者：
Sinigaglia F
影响因子：
56.9
作者：
FREMONT, DH;MATSUMURA, M;WILSON, IA
通讯作者：
WILSON, IA