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

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.

journal_name

Blood

journal_title

Blood

authors

Geldmacher C,Metzler IS,Tovanabutra S,Asher TE,Gostick E,Ambrozak DR,Petrovas C,Schuetz A,Ngwenyama N,Kijak G,Maboko L,Hoelscher M,McCutchan F,Price DA,Douek DC,Koup RA

doi

10.1182/blood-2009-02-206193

subject

Has Abstract

pub_date

2009-08-20 00:00:00

pages

1553-62

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2009-02-206193

journal_volume

114

pub_type

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