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J Immunol. 2013 Jan 15;190(2):513-8. doi: 10.4049/jimmunol.1201891.

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

Author information

1
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. mangalam.ashutosh@mayo.edu

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.

PMID:
23293357
PMCID:
PMC3545203
DOI:
10.4049/jimmunol.1201891
[Indexed for MEDLINE]
Free PMC Article
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