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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Published on: February 28, 2019

Major histocompatibility complex genomics and human disease.

John Trowsdale1, Julian C Knight

  • 1Department of Pathology and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 1QP, United Kingdom;

Annual Review of Genomics and Human Genetics
|July 24, 2013
PubMed
Summary
This summary is machine-generated.

Genomic analysis of the human major histocompatibility complex (MHC) reveals numerous disease associations. Understanding the functional impact of these MHC variants on immunity and complex diseases remains a key challenge.

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Area of Science:

  • Genomics
  • Immunology
  • Human Genetics

Background:

  • The human major histocompatibility complex (MHC) is a gene-dense, polymorphic region critical for immunity.
  • Genomic analyses have identified numerous MHC associations with various diseases over decades.
  • The MHC encodes proteins vital for antigen processing and presentation, influencing immune responses.

Purpose of the Study:

  • To explore the successes and challenges in interpreting MHC-disease associations.
  • To highlight the role of MHC variants in infectious and autoimmune diseases.
  • To discuss potential indirect associations of MHC with non-infectious/autoimmune conditions like cancers and neuropathies.

Main Methods:

  • Single-nucleotide polymorphism (SNP) genotyping.
  • Human leukocyte antigen (HLA) imputation.
  • High-throughput sequencing for large sample set screening.

Main Results:

  • MHC genomic analysis has successfully identified many disease associations.
  • Class I and class II MHC molecules are crucial for infection resistance.
  • Specific class I and class II alleles are associated with autoimmune conditions.
  • MHC associations extend to cancers and neuropathies, potentially indirectly.

Conclusions:

  • Interpreting the functional significance of MHC variants in disease remains challenging.
  • MHC variation is strongly influenced by infectious disease pressures.
  • Further research is needed to elucidate the complex interplay between MHC, infections, autoimmunity, and other diseases.