Role of disulfide bonds in regulating antigen processing and epitope selection

Ping Li, M. Azizul Haque, Janice Blum

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Knowledge of the events governing Ag processing and epitope selection within APC is key to the development of novel immunotherapeutic strategies for infectious diseases, cancer, and autoimmunity. The influence of disulfides and Ag reduction on the hierarchy of epitope presentation via MHC class II molecules was investigated through studies of a self Ag, IgG κ. HLA-DR4+ B cells preferentially present an immunodominant IgG-derived epitope, κI, relative to a subdominant κII peptide. κI contains a cysteine masked within the native Ag via an intrachain disulfide, the latter of which is reduced during Ag processing. Mutagenesis of this cysteine as well as others within κ minimally perturbed the abundance and overall conformation of IgG. Yet, disruptions in disulfide bonding within this Ag influenced the selective display of class II-restricted dominant and subdominant T cell epitopes. Presentation of the κI epitope from both native and variant IgG was dependent upon cellular expression of IFN-γ-inducible lysosomal thiol reductase. These studies indicate that disulfide bonds regulate Ag processing both locally and at distant sites, thus influencing epitope selection within the class II pathway.

Original languageEnglish (US)
Pages (from-to)2444-2450
Number of pages7
JournalJournal of Immunology
Volume169
Issue number5
StatePublished - Sep 1 2002
Externally publishedYes

Fingerprint

Antigen Presentation
Disulfides
Epitopes
Immunoglobulin G
Cysteine
HLA-DR4 Antigen
T-Lymphocyte Epitopes
HLA-B Antigens
Autoimmunity
Sulfhydryl Compounds
Mutagenesis
Communicable Diseases
Oxidoreductases
B-Lymphocytes
Peptides
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Role of disulfide bonds in regulating antigen processing and epitope selection. / Li, Ping; Haque, M. Azizul; Blum, Janice.

In: Journal of Immunology, Vol. 169, No. 5, 01.09.2002, p. 2444-2450.

Research output: Contribution to journalArticle

Li, Ping ; Haque, M. Azizul ; Blum, Janice. / Role of disulfide bonds in regulating antigen processing and epitope selection. In: Journal of Immunology. 2002 ; Vol. 169, No. 5. pp. 2444-2450.
@article{2eca6cb0ae174a7cadd716a60b127bdb,
title = "Role of disulfide bonds in regulating antigen processing and epitope selection",
abstract = "Knowledge of the events governing Ag processing and epitope selection within APC is key to the development of novel immunotherapeutic strategies for infectious diseases, cancer, and autoimmunity. The influence of disulfides and Ag reduction on the hierarchy of epitope presentation via MHC class II molecules was investigated through studies of a self Ag, IgG κ. HLA-DR4+ B cells preferentially present an immunodominant IgG-derived epitope, κI, relative to a subdominant κII peptide. κI contains a cysteine masked within the native Ag via an intrachain disulfide, the latter of which is reduced during Ag processing. Mutagenesis of this cysteine as well as others within κ minimally perturbed the abundance and overall conformation of IgG. Yet, disruptions in disulfide bonding within this Ag influenced the selective display of class II-restricted dominant and subdominant T cell epitopes. Presentation of the κI epitope from both native and variant IgG was dependent upon cellular expression of IFN-γ-inducible lysosomal thiol reductase. These studies indicate that disulfide bonds regulate Ag processing both locally and at distant sites, thus influencing epitope selection within the class II pathway.",
author = "Ping Li and Haque, {M. Azizul} and Janice Blum",
year = "2002",
month = "9",
day = "1",
language = "English (US)",
volume = "169",
pages = "2444--2450",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Role of disulfide bonds in regulating antigen processing and epitope selection

AU - Li, Ping

AU - Haque, M. Azizul

AU - Blum, Janice

PY - 2002/9/1

Y1 - 2002/9/1

N2 - Knowledge of the events governing Ag processing and epitope selection within APC is key to the development of novel immunotherapeutic strategies for infectious diseases, cancer, and autoimmunity. The influence of disulfides and Ag reduction on the hierarchy of epitope presentation via MHC class II molecules was investigated through studies of a self Ag, IgG κ. HLA-DR4+ B cells preferentially present an immunodominant IgG-derived epitope, κI, relative to a subdominant κII peptide. κI contains a cysteine masked within the native Ag via an intrachain disulfide, the latter of which is reduced during Ag processing. Mutagenesis of this cysteine as well as others within κ minimally perturbed the abundance and overall conformation of IgG. Yet, disruptions in disulfide bonding within this Ag influenced the selective display of class II-restricted dominant and subdominant T cell epitopes. Presentation of the κI epitope from both native and variant IgG was dependent upon cellular expression of IFN-γ-inducible lysosomal thiol reductase. These studies indicate that disulfide bonds regulate Ag processing both locally and at distant sites, thus influencing epitope selection within the class II pathway.

AB - Knowledge of the events governing Ag processing and epitope selection within APC is key to the development of novel immunotherapeutic strategies for infectious diseases, cancer, and autoimmunity. The influence of disulfides and Ag reduction on the hierarchy of epitope presentation via MHC class II molecules was investigated through studies of a self Ag, IgG κ. HLA-DR4+ B cells preferentially present an immunodominant IgG-derived epitope, κI, relative to a subdominant κII peptide. κI contains a cysteine masked within the native Ag via an intrachain disulfide, the latter of which is reduced during Ag processing. Mutagenesis of this cysteine as well as others within κ minimally perturbed the abundance and overall conformation of IgG. Yet, disruptions in disulfide bonding within this Ag influenced the selective display of class II-restricted dominant and subdominant T cell epitopes. Presentation of the κI epitope from both native and variant IgG was dependent upon cellular expression of IFN-γ-inducible lysosomal thiol reductase. These studies indicate that disulfide bonds regulate Ag processing both locally and at distant sites, thus influencing epitope selection within the class II pathway.

UR - http://www.scopus.com/inward/record.url?scp=0036721601&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036721601&partnerID=8YFLogxK

M3 - Article

C2 - 12193713

AN - SCOPUS:0036721601

VL - 169

SP - 2444

EP - 2450

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -