Human Leukocyte Antigen (HLA) in Adaptive Immune Response
The Major Histocompatibility Complex (MHC) comprises a number of genes that occur in many species. The encoded proteins help the adaptive immune system to tell the body's own proteins apart from those of pathogens such as viruses, bacteria, and protozoans. In humans, MHC proteins are encoded by the Human Leukocyte Antigen (HLA), a group of more than 200 genes located closely together on the short arm of chromosome 6.
MHC class I complexes are heterodimers consisting of a polymorphic α heavy chain and an invariant β2 microtubulin chain. Genes encoding the α heavy chain are situated within the MHC class I locus whereas the β2 microtubulin genes are typically found outside of this region. The α heavy chain is structurally separated into three N-terminal extracellular domain, α1, α2, and α3, a transmembrane domain, and a short C-terminal cytoplasmic region. Domains α1 and α2 form the peptide-binding groove where peptides from endogenously synthesized proteins are presented to CD8+ cytotoxic T cells.
MHC class II complexes are heterodimers consisting of two polymorphic chains, α and β, each with two domains. The corresponding genes for both subunits are situated within the MHC class II locus. The peptide-binding groove in MHC class II complexes is formed by domains α1 and β1 and peptides are derived from exogenous proteins and presented to CD4+ helper T cells. Upon binding of the epitope by naïve helper T cells, they are primed and undergo polarization into effector or memory Th or Treg cells.
A third cluster of HLAs (MHC class III) between the class I and class II MHC genes encodes components of the complement system and is not involved in the adaptive immune response.
Classical class I and class II MHC are leading candidates for infectious disease susceptibility. Many observations point to a major role in determining susceptibility to viral infections. Individuals with the allele HLA-B*46:01 for example have been shown to have the fewest predicted binding peptides for SARS and SARS-CoV-2. A different allele, HLA-B*15:03, shows the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting it could enable cross-protective T-cell based immunity.These observations point towards a potential influence of different HLA composition - the haplotype - in the situations such as the SARS-CoV-2 pandemic. Association of various HLA haplotypes with SARS-CoV-2 susceptibility and the course of COVID-19 could allow strategizing prevention, treatment, vaccination, and optimizing clinical approaches.
Browse our portfolio of HLA antibodies below! Some antibodies recognize several HLA molecues; for example the MHC Class II antibody based on clone IVA12 recognizes the shared epitopes of human leucocyte antigen (HLA) class II molecules HLA-DP, HLA-DQ and HLA-DR heterodimeric cell surface glycoproteins comprised of an α heavy chain and a β light chain.
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References:
- : "HLA and infectious diseases." in: Clinical microbiology reviews, Vol. 22, Issue 2, pp. 370-85, Table of Contents, (2009) (PubMed).
- : "Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2." in: Journal of virology, Vol. 94, Issue 13, (2020) (PubMed).
- : "COVID-19 infection: the perspectives on immune responses." in: Cell death and differentiation, Vol. 27, Issue 5, pp. 1451-1454, (2020) (PubMed).
