HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile

Ashutosh K Mangalam; Veena Taneja; Chella S David

doi:10.4049/jimmunol.1201891

Back

Journal article

Peer reviewed

HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile

Ashutosh K Mangalam, Veena Taneja and Chella S David

Journal of immunology (Baltimore, Md. : 1950), Vol.190(2), pp.513-518

01/15/2013

DOI: 10.4049/jimmunol.1201891

PMCID: PMC3545203

PMID: 23293357

View Online

Abstract

The MHC in humans encodes the most polymorphic genes, the HLA genes, which are critical for the immune system to clear infection. This can be attributed to strong selection pressure as populations moved to different parts of the world and encountered new kinds of infections, leading to new HLA class II alleles. HLA genes also have the highest relative risk for autoimmune diseases. Three haplotypes, that is, HLA-DR2DQ6, DR4DQ8, and DR3DQ2, account for HLA association with most autoimmune diseases. We hypothesize that these haplotypes, along with their multiple subtypes, have survived bottlenecks of infectious episodes in human history because of their ability to present pathogenic peptides to activate T cells that secrete cytokines to clear infections. Unfortunately, they also present self-peptides/mimics to activate autoreactive T cells secreting proinflammatory cytokines that cause autoimmune diseases.

Haplotypes

T-Lymphocyte Subsets

Cytokines - metabolism

HLA-D Antigens - genetics

Humans

Autoimmune Diseases - immunology

Autoimmunity - genetics

Autoimmune Diseases - prevention & control

HLA-D Antigens - immunology

Autoimmune Diseases - genetics

CD4-Positive T-Lymphocytes - immunology

Animals

Disease Susceptibility - immunology

Autoimmunity - immunology

Details

Title: Subtitle: HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile
Creators: Ashutosh K Mangalam - Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. mangalam.ashutosh@mayo.edu
Veena Taneja
Chella S David
Resource Type: Journal article
Publication Details: Journal of immunology (Baltimore, Md. : 1950), Vol.190(2), pp.513-518
DOI: 10.4049/jimmunol.1201891
PMID: 23293357
PMCID: PMC3545203
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R21 AR060077 / NIAMS NIH HHS R01 AR030752 / NIAMS NIH HHS AR60077 / NIAMS NIH HHS R01 AI075262 / NIAID NIH HHS AR30752 / NIAMS NIH HHS R01 NS052173 / NINDS NIH HHS R56 AR030752 / NIAMS NIH HHS AI75262 / NIAID NIH HHS NS52173 / NINDS NIH HHS
Language: English
Date published: 01/15/2013
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9983905518802771

Metrics

13 Record Views

100 Times Cited - Web of Science