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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 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. Class I HLAs present peptides from inside the cell whereas class II HLAs present antigens from outside of the cell to T-lymphocytes. A third cluster of HLAs (class III HLAs), situated between class I and class II HLAs, encodes components of the complement system and is not involved in the adaptive immune response.

Classical class I and class II Human Leukocyte Antigen (HLA) are leading candidates for infectious disease susceptibility. Many observations point to a major role for classical HLA loci in determining susceptibility to viral infections1. A recent study shows that individuals with the allele HLA-B*46:01 have the fewest predicted binding peptides for SARS-CoV-2, suggesting they may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS. A different allele, HLA-B*15:03, showed 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. 2 These observations point towards a potential influence of different HLA composition - the haplotype - in the present SARS-CoV-2 pandemic. Association of various HLA haplotypes with SARS-CoV-2 infection and the course of COVID-19 could improve assessment of viral severity in the population. Thus, it could allow strategizing prevention, treatment, vaccination, and optimizing clinical approaches3.

Additional SARS-CoV-2 Resources:

References:

  1. Blackwell, Jamieson, Burgner (2009) "HLA and infectious diseases" Clin Microbiol Rev.; 22(2):370-85
  2. Nguyen et al. (2020) "Human leukocyte antigen susceptibility map for SARS-CoV-2"; medRxiv
  3. Shi et al. (2020) "COVID-19 infection: the perspectives on immune responses" Cell Death Differ. (ePrint)

HLA Class I Genes

HLA Class II Genes

HLA-DRB3 (Major Histocompatibility Complex, Class II, DR beta 3):

HLA-DRB4 - Major Histocompatibility Complex, Class II, DR beta 4:

HLA-DQA1 - Major Histocompatibility Complex, Class II, DQ alpha 1:

HLA-DPA1 - Major Histocompatibility Complex, Class II, DP alpha 1:

HLA-DPB1 (Major Histocompatibility Complex, Class II, DP beta 1):

HLA-DMB (Major Histocompatibility Complex, Class II, DM beta):

HLA-DOB (Major Histocompatibility Complex, Class II, DO beta):

HLA Class I Pseudogenes

HLA-H (Major Histocompatibility Complex, Class I, H (Pseudogene)):

Other Genes within the MHC

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