PMID- 26392055
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20181113
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 86
IP  - 5
DP  - 2015 Nov
TI  - A limit to the divergent allele advantage model supported by variable pathogen 
      recognition across HLA-DRB1 allele lineages.
PG  - 343-52
LID - 10.1111/tan.12667 [doi]
AB  - Genetic diversity in human leukocyte antigen (HLA) molecules is thought to have 
      arisen from the co-evolution between host and pathogen and maintained by 
      balancing selection. Heterozygote advantage is a common proposed scenario for 
      maintaining high levels of diversity in HLA genes, and extending from this, the 
      divergent allele advantage (DAA) model suggests that individuals with more 
      divergent HLA alleles bind and recognize a wider array of antigens. While the DAA 
      model seems biologically suitable for driving HLA diversity, there is likely an 
      upper threshold to the amount of sequence divergence. We used peptide-binding and 
      pathogen-recognition capacity of DRB1 alleles as a model to further explore the 
      DAA model; within the DRB1 locus, we examined binding predictions based on two 
      distinct phylogenetic groups (denoted group A and B) previously identified based 
      on non-peptide-binding region (PBR) nucleotide sequences. Predictions in this 
      study support that group A allele and group B allele lineages have contrasting 
      binding/recognition capacity, with only the latter supporting the DAA model. 
      Furthermore, computer simulations revealed an inconsistency in the DAA model 
      alone with observed extent of polymorphisms, supporting that the DAA model could 
      only work effectively in combination with other mechanisms. Overall, we support 
      that the mechanisms driving HLA diversity are non-exclusive. By investigating the 
      relationships among HLA alleles, and pathogens recognized, we can provide further 
      insights into the mechanisms on how humans have adapted to infectious diseases 
      over time.
CI  - (c) 2015 The Authors. Tissue Antigens published by John Wiley & Sons Ltd.
FAU - Lau, Q
AU  - Lau Q
AD  - Department of Evolutionary Studies of Biosystems, Sokendai (The Graduate 
      University for Advanced Studies), Kanagawa, Japan.
FAU - Yasukochi, Y
AU  - Yasukochi Y
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, Tokyo, Japan.
FAU - Satta, Y
AU  - Satta Y
AD  - Department of Evolutionary Studies of Biosystems, Sokendai (The Graduate 
      University for Advanced Studies), Kanagawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150922
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - *Alleles
MH  - Antigen Presentation/*genetics
MH  - *Computer Simulation
MH  - Female
MH  - Genetic Loci/*immunology
MH  - *HLA-DRB1 Chains/genetics/immunology
MH  - Humans
MH  - Male
MH  - *Models, Genetic
MH  - *Models, Immunological
PMC - PMC5054888
OTO - NOTNLM
OT  - allele divergence
OT  - human leukocyte antigen
OT  - major histocompatibility complex
OT  - pathogen recognition
EDAT- 2015/09/24 06:00
MHDA- 2016/08/02 06:00
PMCR- 2016/10/07
CRDT- 2015/09/23 06:00
PHST- 2015/03/09 00:00 [received]
PHST- 2015/08/24 00:00 [revised]
PHST- 2015/08/26 00:00 [accepted]
PHST- 2015/09/23 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
PHST- 2016/10/07 00:00 [pmc-release]
AID - TAN12667 [pii]
AID - 10.1111/tan.12667 [doi]
PST - ppublish
SO  - Tissue Antigens. 2015 Nov;86(5):343-52. doi: 10.1111/tan.12667. Epub 2015 Sep 22.