The Impact of HLA-B Micropolymorphism Outside Primary Peptide Anchor Pockets on the CTL Response to CMV

Burrows, J.M., Wynn, K.K., Tynan, F.E., Archbold, J., Miles, J.J., Bell, M.J., Brennan, R.M., Walker, S., McCluskey, J., Rossjohn, J., Khanna, R. and Burrows, S.R. (2007) The Impact of HLA-B Micropolymorphism Outside Primary Peptide Anchor Pockets on the CTL Response to CMV. European Journal of Immunology, 37 4: 946-953. doi:10.1002/eji.200636588

Author Burrows, J.M.
Wynn, K.K.
Tynan, F.E.
Archbold, J.
Miles, J.J.
Bell, M.J.
Brennan, R.M.
Walker, S.
McCluskey, J.
Rossjohn, J.
Khanna, R.
Burrows, S.R.
Title The Impact of HLA-B Micropolymorphism Outside Primary Peptide Anchor Pockets on the CTL Response to CMV
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1002/eji.200636588
Open Access Status DOI
Volume 37
Issue 4
Start page 946
End page 953
Total pages 8
Place of publication Weinheim, Germany
Publisher Wiley-V C H Verlag Gmbh & Co. KGaA
Language eng
Subject 321010 Infectious Diseases
730102 Immune system and allergy
Abstract The factors controlling epitope selection in the T cell response to persistent viruses are not fully understood, and we have examined this issue in the context of four HLA-B*35binding peptides from the pp65 antigen of human cytomegalovirus, two of which are previously undescribed. Striking differences in the hierarchy of immunodominance between these four epitopes were observed in healthy virus carriers expressing HLAB*3501 versus B*3508, two HLA-B allotypes that differ by a single amino acid at position 156 (HLA-B*3501, (156)Leucine; HLA-B*3508, (156)Arginine) that projects from the alpha 2 helix into the centre of the peptide-binding groove. While HLA-B*3501(+) individuals responded most strongly to the (IPSINVHHY131)-I-123 and (366)HPTFTSQY(373) epitopes, HLAB*3508(+) individuals responded preferentially to (103)CPSQEPMSIYVY(114) and (188)FPTKDVAL(195) . By comparing peptide-MHC association and disassociation rates with peptide immunogenicity, it was clear that dissociation rates correlate more closely with the hierarchy of immunodominance among the four pp65 peptides. These findings demonstrate that MHC micropolymorphism at positions outside the primary anchor residue binding pockets can have a major impact on determinant selection in antiviral T cell responses. Such influences may provide the evolutionary pressure that maintains closely related MHC molecules in diverse human populations.
Keyword Immunology
antigen presentation
cytotoxic T cells
Human Cytomegalovirus-infection
T-lymphocyte Responses
Class-i Molecules
Complex Class-i
Hla-b27 Subtypes
Viral Epitope
Cell Recognition
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2008 Higher Education Research Data Collection
School of Public Health Publications
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Citation counts: TR Web of Science Citation Count  Cited 34 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 35 times in Scopus Article | Citations
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Created: Tue, 19 Feb 2008, 02:55:47 EST