PMID- 20934997
OWN - NLM
STAT- MEDLINE
DCOM- 20110526
LR  - 20211020
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 96
IP  - 1
DP  - 2011 Jan
TI  - The impact of human leukocyte antigen (HLA) micropolymorphism on ligand 
      specificity within the HLA-B*41 allotypic family.
PG  - 110-8
LID - 10.3324/haematol.2010.030924 [doi]
AB  - BACKGROUND: Polymorphic differences between human leukocyte antigen (HLA) 
      molecules affect the specificity and conformation of their bound peptides and 
      lead to differential selection of the T-cell repertoire. Mismatching during 
      allogeneic transplantation can, therefore, lead to immunological reactions. 
      DESIGN AND METHODS: We investigated the structure-function relationships of six 
      members of the HLA-B*41 allelic group that differ by six polymorphic amino acids, 
      including positions 80, 95, 97 and 114 within the antigen-binding cleft. 
      Peptide-binding motifs for B*41:01, *41:02, *41:03, *41:04, *41:05 and *41:06 
      were determined by sequencing self-peptides from recombinant B*41 molecules by 
      electrospray ionization tandem mass spectrometry. The crystal structures of 
      HLA-B*41:03 bound to a natural 16-mer self-ligand (AEMYGSVTEHPSPSPL) and 
      HLA-B*41:04 bound to a natural 11-mer self-ligand (HEEAVSVDRVL) were solved. 
      RESULTS: Peptide analysis revealed that all B*41 alleles have an identical anchor 
      motif at peptide position 2 (glutamic acid), but differ in their choice of 
      C-terminal pOmega anchor (proline, valine, leucine). Additionally, B*41:04 displayed 
      a greater preference for long peptides (>10 residues) when compared to the other 
      B*41 allomorphs, while the longest peptide to be eluted from the allelic group (a 
      16mer) was obtained from B*41:03. The crystal structures of HLA-B*41:03 and 
      HLA-B*41:04 revealed that both alleles interact in a highly conserved manner with 
      the terminal regions of their respective ligands, while micropolymorphism-induced 
      changes in the steric and electrostatic properties of the antigen-binding cleft 
      account for differences in peptide repertoire and auxiliary anchoring. 
      CONCLUSIONS: Differences in peptide repertoire, and peptide length specificity 
      reflect the significant functional evolution of these closely related allotypes 
      and signal their importance in allogeneic transplantation, especially B*41:03 and 
      B*41:04, which accommodate longer peptides, creating structurally distinct 
      peptide-HLA complexes.
FAU - Bade-Doding, Christina
AU  - Bade-Doding C
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Theodossis, Alex
AU  - Theodossis A
FAU - Gras, Stephanie
AU  - Gras S
FAU - Kjer-Nielsen, Lars
AU  - Kjer-Nielsen L
FAU - Eiz-Vesper, Britta
AU  - Eiz-Vesper B
FAU - Seltsam, Axel
AU  - Seltsam A
FAU - Huyton, Trevor
AU  - Huyton T
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - McCluskey, James
AU  - McCluskey J
FAU - Blasczyk, Rainer
AU  - Blasczyk R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101007
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B41 antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Epitopes, T-Lymphocyte/*genetics
MH  - HLA-B Antigens/chemistry/*genetics/metabolism
MH  - Humans
MH  - Peptide Fragments/*immunology/metabolism
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Protein Binding
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry/*genetics/metabolism
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - T-Lymphocytes, Cytotoxic/immunology
PMC - PMC3012774
EDAT- 2010/10/12 06:00
MHDA- 2011/05/27 06:00
PMCR- 2011/01/01
CRDT- 2010/10/12 06:00
PHST- 2010/10/12 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/05/27 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - haematol.2010.030924 [pii]
AID - 0960110 [pii]
AID - 10.3324/haematol.2010.030924 [doi]
PST - ppublish
SO  - Haematologica. 2011 Jan;96(1):110-8. doi: 10.3324/haematol.2010.030924. Epub 2010 
      Oct 7.