PMID- 19930454
OWN - NLM
STAT- MEDLINE
DCOM- 20100927
LR  - 20100618
IS  - 1558-5646 (Electronic)
IS  - 0014-3820 (Linking)
VI  - 64
IP  - 5
DP  - 2010 May
TI  - Identifying coevolutionary patterns in human leukocyte antigen (HLA) molecules.
PG  - 1429-45
LID - 10.1111/j.1558-5646.2009.00903.x [doi]
AB  - The antigenic peptide, major histocompatibility complex molecule (MHC; also 
      called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor 
      (TCR) function as a complex to initiate effectors' mechanisms of the immune 
      system. The tight functional and physical interaction among these molecules may 
      have involved strong coevolution links among domains within and between proteins. 
      Despite the importance of unraveling such dependencies to understand the arms 
      race of host-pathogen interaction, no previous studies have aimed at achieving 
      such an objective. Here, we perform an exhaustive coevolution analysis and show 
      that indeed such dependencies are strongly shaping the evolution and probably the 
      function of these molecules. We identify intramolecular coevolution in HLA class 
      I and II at domains important for their immune activity. Most of the amino acid 
      sites identified to be coevolving in HLAI have been also detected to undergo 
      positive Darwinian selection highlighting therefore their adaptive value. We also 
      identify coevolution among antigen-binding pockets (P1-P9) and among these and 
      TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our 
      results support that such coevolutionary patterns are due to selective pressures 
      of host-pathogen coevolution and cooperative binding of TCRs, antigenic peptides, 
      and CD8/CD4 to HLAI and HLAII.
FAU - Jiang, Xiaowei
AU  - Jiang X
AD  - Evolutionary Genetics and Bioinformatics Laboratory, Department of Genetics, 
      Smurfit Institute of Genetics, University of Dublin, Trinity College Dublin, 
      Dublin 2, Ireland. jiangx@tcd.ie
FAU - Fares, Mario A
AU  - Fares MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091120
PL  - United States
TA  - Evolution
JT  - Evolution; international journal of organic evolution
JID - 0373224
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Evolution, Molecular
MH  - HLA Antigens/*genetics
MH  - Humans
EDAT- 2009/11/26 06:00
MHDA- 2010/09/29 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/09/29 06:00 [medline]
AID - EVO903 [pii]
AID - 10.1111/j.1558-5646.2009.00903.x [doi]
PST - ppublish
SO  - Evolution. 2010 May;64(5):1429-45. doi: 10.1111/j.1558-5646.2009.00903.x. Epub 
      2009 Nov 20.