TCR contact residue hydrophobicity is a hallmark of immunogenic CD8<sup>+</sup> T cell epitopes

Diego Chowell, Sri Krishna, Pablo D. Becker, Clément Cocita, Jack Shu, Xuefang Tan, Philip D. Greenberg, Linda S. Klavinskis, Joseph Blattman, Karen Anderson

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8<sup>+</sup> T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.

Original languageEnglish (US)
Pages (from-to)E1754-E1762
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number14
DOIs
StatePublished - Apr 7 2015

Fingerprint

T-Lymphocyte Epitopes
Hydrophobic and Hydrophilic Interactions
Epitopes
Major Histocompatibility Complex
Peptides
Vaccines
T-Lymphocytes
gag Gene Products
Antigens
Neoplasm Antigens
T-Cell Antigen Receptor
HIV-1
Amino Acids

Keywords

  • Epitope prediction
  • Immunogenicity
  • MHC class I
  • Nonself
  • T cell
  • Vaccine

ASJC Scopus subject areas

  • General

Cite this

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8<sup>+</sup> T cell epitopes. / Chowell, Diego; Krishna, Sri; Becker, Pablo D.; Cocita, Clément; Shu, Jack; Tan, Xuefang; Greenberg, Philip D.; Klavinskis, Linda S.; Blattman, Joseph; Anderson, Karen.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 14, 07.04.2015, p. E1754-E1762.

Research output: Contribution to journalArticle

Chowell, Diego ; Krishna, Sri ; Becker, Pablo D. ; Cocita, Clément ; Shu, Jack ; Tan, Xuefang ; Greenberg, Philip D. ; Klavinskis, Linda S. ; Blattman, Joseph ; Anderson, Karen. / TCR contact residue hydrophobicity is a hallmark of immunogenic CD8<sup>+</sup> T cell epitopes. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 14. pp. E1754-E1762.
@article{12a6edc8cc794f4e918493091e9b9013,
title = "TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes",
abstract = "Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8+ T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.",
keywords = "Epitope prediction, Immunogenicity, MHC class I, Nonself, T cell, Vaccine",
author = "Diego Chowell and Sri Krishna and Becker, {Pablo D.} and Cl{\'e}ment Cocita and Jack Shu and Xuefang Tan and Greenberg, {Philip D.} and Klavinskis, {Linda S.} and Joseph Blattman and Karen Anderson",
year = "2015",
month = "4",
day = "7",
doi = "10.1073/pnas.1500973112",
language = "English (US)",
volume = "112",
pages = "E1754--E1762",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

TY - JOUR

T1 - TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes

AU - Chowell, Diego

AU - Krishna, Sri

AU - Becker, Pablo D.

AU - Cocita, Clément

AU - Shu, Jack

AU - Tan, Xuefang

AU - Greenberg, Philip D.

AU - Klavinskis, Linda S.

AU - Blattman, Joseph

AU - Anderson, Karen

PY - 2015/4/7

Y1 - 2015/4/7

N2 - Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8+ T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.

AB - Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8+ T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.

KW - Epitope prediction

KW - Immunogenicity

KW - MHC class I

KW - Nonself

KW - T cell

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=84929659335&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929659335&partnerID=8YFLogxK

U2 - 10.1073/pnas.1500973112

DO - 10.1073/pnas.1500973112

M3 - Article

VL - 112

SP - E1754-E1762

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -