Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues

被引：23

作者：

Kubiniok, Peter ^{[1
]}

Marcu, Ana ^{[2
,3
]}

Bichmann, Leon ^{[2
,4
]}

Kuchenbecker, Leon ^{[4
]}

Schuster, Heiko ^{[5
]}

Hamelin, David J. ^{[1
]}

Duquette, Jerome D. ^{[1
]}

Kovalchik, Kevin A. ^{[1
]}

Wessling, Laura ^{[1
]}

Kohlbacher, Oliver ^{[4
,7
,8
,9
,10
]}

Rammensee, Hans-Georg ^{[2
,3
,6
]}

Neidert, Marian C. ^{[11
,12
,13
,14
,15
,16
]}

Sirois, Isabelle ^{[1
]}

Caron, Etienne ^{[1
,17
]}

机构：

[1] CHU St Justine Res Ctr, Montreal, PQ H3T 1C5, Canada

[2] Univ Tubingen, Interfac Inst Cell Biol, Dept Immunol, D-72076 Tubingen, Baden Wurttembe, Germany

[3] Univ Tubingen, Cluster Excellence iFIT EXC 2180, Image Guided & Funct Instructed Tumor Therapies, D-72076 Tubingen, Baden Wurttembe, Germany

[4] Univ Tubingen, Appl Bioinformat, Dept Comp Sci, D-72074 Tubingen, Baden Wurttembe, Germany

[5] Immat Biotechnol GmbH, D-72076 Tubingen, Baden Wurttembe, Germany

[6] German Canc Consortium DKTK, DKFZ Partner Site Tubingen, D-72076 Tubingen, Baden Wurttembe, Germany

[7] Univ Tubingen, Inst Bioinformat & Med Informat, D-72076 Tubingen, Baden Wurttembe, Germany

[8] Max Planck Inst Dev Biol, Biomol Interact, D-72076 Tubingen, Baden Wurttembe, Germany

[9] Univ Tubingen, Cluster Excellence Machine Learning Sci EXC 2064, D-72076 Tubingen, Baden Wurttembe, Germany

[10] Univ Hosp Tubingen, Translat Bioinformat, D-72076 Tubingen, Baden Wurttembe, Germany

[11] Univ Hosp, Clin Neurosci Ctr, CH-8057 Zurich, Switzerland

[12] Univ Hosp, Dept Neurosurg, CH-8057 Zurich, Switzerland

[13] Univ Zurich, CH-8057 Zurich, Switzerland

[14] Univ Hosp, Clin Neurosci Ctr, CH-8091 Zurich, Switzerland

[15] Univ Hosp, Dept Neurosurg, CH-8091 Zurich, Switzerland

[16] Univ Zurich, CH-8091 Zurich, Switzerland

[17] Univ Montreal, Dept Pathol & Cellular Biol, Fac Med, Montreal, PQ H3T 1J4, Canada

来源：

ISCIENCE | 2022年 / 25卷 / 02期

基金：

加拿大创新基金会; 加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

PEPTIDE REPERTOIRE; MASS-SPECTROMETRY; R-PACKAGE; REVEALS; EXPRESSION; SHAPES; AMINOPEPTIDASE; GENERATION; PRODUCTS; ENABLES;

D O I：

10.1016/j.isci.2022.103768

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Understanding the molecular principles that govern the composition of the MHCI immunopeptidome across different primary tissues is fundamentally important to predict how T cells respond in different contexts in vivo. Here, we performed a global analysis of the MHC-I immunopeptidome from 29 to 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, HLA-B, and HLA-C allotypes do not contribute evenly to the global composition of the MHC-I immunopeptidome across multiple human tissues. Second, we found that tissue specific and housekeeping MHC-I peptides share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-I immunopeptidome at the organism-wide scale. Fourth, we uncovered new components of the antigen processing and presentation network, including the carboxypeptidases CPE, CNDP1/2, and CPVL. Together, this study opens up new avenues toward a system-wide understanding of antigen presentation in vivo across mammalian species.

引用

页数：24

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