Immune surveillance for ERAAP dysfunction

Niranjana A. Nagarajan, Nilabh Shastri

Research output: Contribution to journalReview article

Abstract

The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1b, a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1b complex were frequent in naïve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1b complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction.

Original languageEnglish (US)
Pages (from-to)120-122
Number of pages3
JournalMolecular Immunology
Volume55
Issue number2
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

T-Lymphocytes
Peptides
Cytomegalovirus
Endoplasmic Reticulum
Autoimmune Diseases
Immune System
Phenotype
Antigens

Keywords

  • Antigen processing
  • CD8+ T cells
  • Immune surveillance
  • MHC class I

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Immune surveillance for ERAAP dysfunction. / Nagarajan, Niranjana A.; Shastri, Nilabh.

In: Molecular Immunology, Vol. 55, No. 2, 01.09.2013, p. 120-122.

Research output: Contribution to journalReview article

Nagarajan, Niranjana A. ; Shastri, Nilabh. / Immune surveillance for ERAAP dysfunction. In: Molecular Immunology. 2013 ; Vol. 55, No. 2. pp. 120-122.
@article{39699950faca406c819cfb6a4948fbb6,
title = "Immune surveillance for ERAAP dysfunction",
abstract = "The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1b, a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1b complex were frequent in na{\"i}ve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1b complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction.",
keywords = "Antigen processing, CD8+ T cells, Immune surveillance, MHC class I",
author = "Nagarajan, {Niranjana A.} and Nilabh Shastri",
year = "2013",
month = "9",
day = "1",
doi = "10.1016/j.molimm.2012.10.006",
language = "English (US)",
volume = "55",
pages = "120--122",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Immune surveillance for ERAAP dysfunction

AU - Nagarajan, Niranjana A.

AU - Shastri, Nilabh

PY - 2013/9/1

Y1 - 2013/9/1

N2 - The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1b, a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1b complex were frequent in naïve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1b complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction.

AB - The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1b, a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1b complex were frequent in naïve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1b complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction.

KW - Antigen processing

KW - CD8+ T cells

KW - Immune surveillance

KW - MHC class I

UR - http://www.scopus.com/inward/record.url?scp=84875625610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875625610&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2012.10.006

DO - 10.1016/j.molimm.2012.10.006

M3 - Review article

C2 - 23433779

AN - SCOPUS:84875625610

VL - 55

SP - 120

EP - 122

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 2

ER -