Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response

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

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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

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