Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity

被引：84

作者：

Adams, Jarrett J. ^{[1
,2
,3
,4
,5
,8
]}

Narayanan, Samanthi ^{[6
,8
]}

Birnbaum, Michael E. ^{[1
,2
,3
,8
]}

Sidhu, Sachdev S. ^{[4
,5
]}

Blevins, Sydney J. ^{[7
]}

Gee, Marvin H. ^{[1
,2
,3
]}

Sibener, Leah V. ^{[1
,2
,3
]}

Baker, Brian M. ^{[7
]}

Kranz, David M. ^{[6
]}

Garcia, K. Christopher ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Mol & Cellular Physiol, Program Immunol, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Biol Struct, Program Immunol, Stanford, CA 94305 USA

[4] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Banting & Best Dept Med Res, Toronto, ON, Canada

[5] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON, Canada

[6] Univ Illinois, Dept Biochem, Urbana, IL USA

[7] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA

[8] Univ Notre Dame, Harper Canc Res Inst, Notre Dame, IN 46556 USA

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 01期

基金：

加拿大健康研究院; 美国国家卫生研究院; 美国国家科学基金会;

关键词：

T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I; DIFFRACTION DATA; AMINO-ACIDS; SPECIFICITY; REPERTOIRE; ANTIGENS; SELF; BIAS;

D O I：

10.1038/ni.3310

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The T cell antigen receptor (TCR)-peptide-major histocompatibility complex (MHC) interface is composed of conserved and diverse regions, yet the relative contribution of each in shaping recognition by T cells remains unclear. Here we isolated cross-reactive peptides with limited homology, which allowed us to compare the structural properties of nine peptides for a single TCR-MHC pair. The TCR's cross-reactivity was rooted in highly similar recognition of an apical 'hot-spot' position in the peptide with tolerance of sequence variation at ancillary positions. Furthermore, we found a striking structural convergence onto a germline-mediated interaction between the TCR CDR1. region and the MHC. 2 helix in twelve TCR-peptide-MHC complexes. Our studies suggest that TCR-MHC germline-mediated constraints, together with a focus on a small peptide hot spot, might place limits on peptide antigen cross-reactivity.

引用

页码：87 / +

页数：10

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