Geldmacher, Christof, Metzler, Ian S., Tovanabutra, Sodsai, Asher, Tedi E., Gostick, Emma, Ambrozak, David R., Petrovas, Constantinos, Schuetz, Alexandra, Ngwenyama, Njabulo, Kijak, Gustavo, Maboko, Leonard, Hoelscher, Michael, McCutchan, Francine, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Douek, Daniel C. and Koup, Richard A. 2009. Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response. Blood 114 (8) , pp. 1553-1562. 10.1182/blood-2009-02-206193 |
Abstract
Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting HLA class I molecule, CD8 T-cell responses elicited by subtype C exhibited largely comparable TL9 variant cross-recognition properties, expressed T-cell receptors that used almost exclusively the TRBV 12-3 gene, and selected for predictable patterns of viral variation within TL9. In contrast, subtype A elicited TL9-specific CD8 T-cell populations with completely different, more diverse TCRBV genes and did not select for viral variants. Moreover, TL9 variant cross-recognition properties were extensive in B81+ subjects but limited in B42+ subjects. Thus, minor viral and host genetic polymorphisms can dramatically alter the immunologic and virologic outcome of an epitope-specific CD8 T-cell response.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Subjects: | Q Science > QR Microbiology > QR180 Immunology |
Publisher: | American Society of Hematology |
ISSN: | 0006-4971 |
Last Modified: | 06 Nov 2022 13:55 |
URI: | https://orca.cardiff.ac.uk/id/eprint/28228 |
Citation Data
Cited 21 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |