Limited maintenance of vaccine-induced simian immunodeficiency virus-specific CD8 T-cell receptor clonotypes after virus challenge.
T-cell receptors (TCRs) govern the specificity, efficacy, and cross-reactivity of CD8 T cells. Here, we studied CD8 T-cell clonotypes from Mane-A*10(+) pigtail macaques responding to the simian immunodeficiency virus (SIV) Gag KP9 epitope in a setting of vaccination and subsequent viral challenge. We observed a diverse TCR repertoire after DNA, recombinant poxvirus, and live attenuated virus vaccination, with none of 59 vaccine-induced KP9-specific TCRs being identical between macaques. The KP9-specific TCR repertoires remained diverse after SIV or simian-human immunodeficiency virus challenge but, remarkably, exhibited substantially different clonotypic compositions compared to the corresponding populations prechallenge. Within serial samples from individual pigtail macaques, only a small subset (33.9%) of TCRs induced by vaccination were maintained or expanded after challenge. Most (66.1%) of the TCRs induced by vaccination were not detectable after challenge. Our results suggest that some CD8 T cells induced by vaccination are more efficient than others at responding to a viral challenge. These findings have implications for future AIDS virus vaccine studies, which should consider the "fitness" of vaccine-induced T cells in order to generate robust responses in the face of virus exposure.
Smith
Miranda Z
MZ
Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia.
Asher
Tedi E
TE
Venturi
Vanessa
V
Davenport
Miles P
MP
Douek
Daniel C
DC
Price
David A
DA
Kent
Stephen J
SJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005787:Gene Frequency; D015683:Gene Products, gag / Q000276:immunology; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology*; D017422:Sequence Analysis, DNA; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
D000939:Epitopes; D015683:Gene Products, gag; D011948:Receptors, Antigen, T-Cell; D018449:SAIDS Vaccines; C115853:simian immunodeficiency virus gag p55