A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition

Macdonald, W. A., Purcell, A. W., Mifsud, N. A., Ely, L. K., Williams, D. S., Chang, L., Gorman, J. J., Clements, C. S., Kjer-Nielsen, L., Koelle, D. M., Burrows, S. R., Tait, B. D., Holdsworth, R., Brooks, A. G., Lovrecz, G. O., Lu, L., Rossjohn, J. and McCluskey, J. (2003) A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition. Journal of Experimental Medicine, 198 5: 679-691. doi:10.1084/jem.20030066

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Author Macdonald, W. A.
Purcell, A. W.
Mifsud, N. A.
Ely, L. K.
Williams, D. S.
Chang, L.
Gorman, J. J.
Clements, C. S.
Kjer-Nielsen, L.
Koelle, D. M.
Burrows, S. R.
Tait, B. D.
Holdsworth, R.
Brooks, A. G.
Lovrecz, G. O.
Lu, L.
Rossjohn, J.
McCluskey, J.
Title A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 2003
Sub-type Article (original research)
DOI 10.1084/jem.20030066
Open Access Status File (Publisher version)
Volume 198
Issue 5
Start page 679
End page 691
Total pages 13
Editor P. L. Bernstein
Place of publication New York
Publisher Rockefeller University Press
Collection year 2003
Language eng
Subject C1
320200 Immunology
730102 Immune system and allergy
Abstract HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a hi,,h frequency in all human populations, and vet they only differ by one residue on the alpha2 helix (B*4402 Aspl56-->B*4403 Leu156) CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphisin at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B 4403 modifies both peptide repertoire and T cell recognition, and is reflected lit the paradoxically powerful alloreactivity that occurs across this minimal mismatch. The findings suggest that these closely related class I genes are maintained lit diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.
Keyword Immunology
Medicine, Research & Experimental
Class 1 Histocompatibility Molecules
Antigen Presentation
X-ray Diffraction
Graft Rejection
Single Amino-acid
Bone-marrow Transplantation
Mhc Polymorphism
Histocompatibility Antigen
Q-Index Code C1
Additional Notes Authors of this document: Macdonald, WA; Purcell, AW; Misfud, NA; Ely, LK; Williams, DS; Chang, LN; Gorman, J; Clements, CS; Kjer-Nielsen, L; Koelle, DM; Burrows, SR; Tait, BD; Holdsworth, R; Brooks, AG; Lovrecz, GO; Lu, L; Rossjohn, J; McCluskey, J.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 132 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 134 times in Scopus Article | Citations
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Created: Tue, 14 Aug 2007, 19:27:27 EST