Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infection.
Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving behind a stable number of memory cells. The relationship between the CD8 T cells that clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-specific CD8 T cells in the mouse model of infection with lymphocytic choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative TCR beta chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR Vbeta-specific antibodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CD8 T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed that CD8 T cells from several Vbeta families participated in the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL) epitope (NP118-126). However, the bulk (approximately 70%) of this CTL response was due to three privileged T cell populations systematically expanding during LCMV infection. Approximately 30% of the response consisted of Vbeta10+ CD8 T cells with a beta chain CDR3 length of nine amino acids, and 40% consisted of Vbeta8.1+ (beta CDR3 = eight amino acids) and Vbeta8.2+ cells (beta CDR3 = six amino acids). Finally, we showed that the TCR repertoire of the primary antiviral CD8 T cell response was similar both structurally and functionally to that of the memory pool and the secondary CD8 T cell effectors. These results suggest a stochastic selection of memory cells from the pool of CD8 T cells activated during primary infection.
Sourdive
D J
DJ
Emory Vaccine Center, Rollins Research Center, Emory University, Atlanta, Georgia 30322, USA.
Murali-Krishna
K
K
Altman
J D
JD
Zajac
A J
AJ
Whitmire
J K
JK
Pannetier
C
C
Kourilsky
P
P
Evavold
B
B
Sette
A
A
Ahmed
R
R
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D004195:Disease Models, Animal; D007137:Immunoglobulin alpha-Chains / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007239:Infections / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D022801:Complementarity Determining Regions; D007137:Immunoglobulin alpha-Chains; D011948:Receptors, Antigen, T-Cell