PMID- 36003377
OWN - NLM
STAT- MEDLINE
DCOM- 20220826
LR  - 20220901
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Human leukocyte antigen class II gene diversity tunes antibody repertoires to 
      common pathogens.
PG  - 856497
LID - 10.3389/fimmu.2022.856497 [doi]
LID - 856497
AB  - Allelic diversity of human leukocyte antigen (HLA) class II genes may help 
      maintain humoral immunity against infectious diseases. In this study, we 
      investigated germline genetic variation in classical HLA class II genes and 
      employed a systematic, unbiased approach to explore the relative contribution of 
      this genetic variation in the antibody repertoire to various common pathogens. We 
      leveraged a well-defined cohort of 800 adults representing the general Arab 
      population in which genetic material is shared because of the high frequency of 
      consanguineous unions. By applying a high-throughput method for large-scale 
      antibody profiling to this well-defined cohort, we were able to dissect the 
      overall effect of zygosity for classical HLA class II genes, as well as the 
      effects associated with specific HLA class II alleles, haplotypes and genotypes, 
      on the antimicrobial antibody repertoire breadth and antibody specificity with 
      unprecedented resolution. Our population genetic studies revealed that zygosity 
      of the classical HLA class II genes is a strong predictor of antibody responses 
      to common human pathogens, suggesting that classical HLA class II gene 
      heterozygosity confers a selective advantage. Moreover, we demonstrated that 
      multiple HLA class II alleles can have additive effects on the antibody 
      repertoire to common pathogens. We also identified associations of HLA-DRB1 
      genotypes with specific antigens. Our findings suggest that HLA class II gene 
      polymorphisms confer specific humoral immunity against common pathogens, which 
      may have contributed to the genetic diversity of HLA class II loci during 
      hominine evolution.
CI  - Copyright (c) 2022 Khan, Rahman, Ahmed, Al Ali, Jithesh and Marr.
FAU - Khan, Taushif
AU  - Khan T
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
FAU - Rahman, Mahbuba
AU  - Rahman M
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
FAU - Ahmed, Ikhlak
AU  - Ahmed I
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
FAU - Al Ali, Fatima
AU  - Al Ali F
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
FAU - Jithesh, Puthen Veettil
AU  - Jithesh PV
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
AD  - College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
FAU - Marr, Nico
AU  - Marr N
AD  - Research Branch, Sidra Medicine, Doha, Qatar.
AD  - College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
LA  - eng
PT  - Journal Article
DEP - 20220808
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adaptive Immunity/genetics
MH  - Adult
MH  - Alleles
MH  - *Antibodies/genetics
MH  - Gene Frequency
MH  - *Genes, MHC Class II/genetics
MH  - *HLA Antigens/genetics
MH  - Haplotypes
MH  - Humans
PMC - PMC9393332
OTO - NOTNLM
OT  - allelic diversity
OT  - association study
OT  - human antibody repertoires
OT  - human leukocyte antigen
OT  - major histocompatibility complex
OT  - microbial infection
OT  - phage immunoprecipitation sequencing
OT  - polymorphisms
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/26 06:00
MHDA- 2022/08/27 06:00
PMCR- 2022/01/01
CRDT- 2022/08/25 02:20
PHST- 2022/01/17 00:00 [received]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2022/08/25 02:20 [entrez]
PHST- 2022/08/26 06:00 [pubmed]
PHST- 2022/08/27 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.856497 [doi]
PST - epublish
SO  - Front Immunol. 2022 Aug 8;13:856497. doi: 10.3389/fimmu.2022.856497. eCollection 
      2022.