Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Burrows, S. R., Elkington, R. A., Miles, J. J., Green, K. J., Walker, S., Haryana, S. M., Moss, D. J., Dunckley, H., Burrows, J. M. and Khanna, R. (2003) Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype. Journal of Immunology, 171 3: 1407-1412.


Author Burrows, S. R.
Elkington, R. A.
Miles, J. J.
Green, K. J.
Walker, S.
Haryana, S. M.
Moss, D. J.
Dunckley, H.
Burrows, J. M.
Khanna, R.
Title Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2003
Sub-type Article (original research)
Volume 171
Issue 3
Start page 1407
End page 1412
Total pages 6
Editor R. Rich
Place of publication Bethesda, U.S.A.
Publisher American Association of Immunologists
Collection year 2003
Language eng
Subject C1
320200 Immunology
730102 Immune system and allergy
1107 Immunology
Abstract Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.
Keyword Immunology
Cytotoxic T-lymphocytes
Virus-associated Diseases
Hla-a Alleles
Peptide Motifs
Cell-receptor
Recombinant Vaccinia
Infected Cells
Binding
Molecules
Identification
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2004 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 14 Aug 2007, 19:30:59 EST