PMID- 19139173
OWN - NLM
STAT- MEDLINE
DCOM- 20090223
LR  - 20211020
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 206
IP  - 1
DP  - 2009 Jan 16
TI  - Natural micropolymorphism in human leukocyte antigens provides a basis for 
      genetic control of antigen recognition.
PG  - 209-19
LID - 10.1084/jem.20082136 [doi]
AB  - Human leukocyte antigen (HLA) gene polymorphism plays a critical role in 
      protective immunity, disease susceptibility, autoimmunity, and drug 
      hypersensitivity, yet the basis of how HLA polymorphism influences T cell 
      receptor (TCR) recognition is unclear. We examined how a natural 
      micropolymorphism in HLA-B44, an important and large HLA allelic family, affected 
      antigen recognition. T cell-mediated immunity to an Epstein-Barr virus 
      determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype 
      compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino 
      acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of 
      binding and dynamics of the bound viral epitope. The structure of the 
      TCR-HLA-B*4405(EENLLDFVRF) complex revealed that peptide flexibility was a 
      critical parameter in enabling preferential engagement with HLA-B*4405 in 
      comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) 
      polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in 
      fine-tuning of T cell responses between closely related allotypes.
FAU - Archbold, Julia K
AU  - Archbold JK
AD  - The Protein Crystallography Unit, Department of Biochemistry and Molecular 
      Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 
      3800, Australia.
FAU - Macdonald, Whitney A
AU  - Macdonald WA
FAU - Gras, Stephanie
AU  - Gras S
FAU - Ely, Lauren K
AU  - Ely LK
FAU - Miles, John J
AU  - Miles JJ
FAU - Bell, Melissa J
AU  - Bell MJ
FAU - Brennan, Rebekah M
AU  - Brennan RM
FAU - Beddoe, Travis
AU  - Beddoe T
FAU - Wilce, Matthew C J
AU  - Wilce MC
FAU - Clements, Craig S
AU  - Clements CS
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - McCluskey, James
AU  - McCluskey J
FAU - Burrows, Scott R
AU  - Burrows SR
FAU - Rossjohn, Jamie
AU  - Rossjohn J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090112
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*44:03 antigen)
RN  - 0 (HLA-B44 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Complementarity Determining Regions/genetics/immunology
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Epstein-Barr Virus Nuclear Antigens/immunology
MH  - HLA Antigens/genetics/metabolism
MH  - HLA-B Antigens/chemistry/*genetics/metabolism
MH  - HLA-B44 Antigen
MH  - Humans
MH  - Hydrogen Bonding
MH  - Kinetics
MH  - Models, Molecular
MH  - *Polymorphism, Single Nucleotide
MH  - Protein Binding
MH  - Protein Conformation
MH  - Receptors, Antigen, T-Cell/genetics/*immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology
MH  - Recombinant Proteins/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
PMC - PMC2626662
EDAT- 2009/01/14 09:00
MHDA- 2009/02/24 09:00
PMCR- 2009/07/19
CRDT- 2009/01/14 09:00
PHST- 2009/01/14 09:00 [entrez]
PHST- 2009/01/14 09:00 [pubmed]
PHST- 2009/02/24 09:00 [medline]
PHST- 2009/07/19 00:00 [pmc-release]
AID - jem.20082136 [pii]
AID - 20082136 [pii]
AID - 10.1084/jem.20082136 [doi]
PST - ppublish
SO  - J Exp Med. 2009 Jan 16;206(1):209-19. doi: 10.1084/jem.20082136. Epub 2009 Jan 
      12.