Predominant clonal accumulation of CD8+ T cells with moderate avidity in the central nervous systems of Theiler's virus-infected C57BL/6 mice.
Induction of antigen-specific CD8(+) T cells bearing a high-avidity T-cell receptor (TCR) is thought to be an important factor in antiviral and antitumor immune responses. However, the relationship between TCR diversity and functional avidity of epitope-specific CD8(+) T cells accumulating in the central nervous system (CNS) during viral infection is unknown. Hence, analysis of T-cell diversity at the clonal level is important to understand the fate and function of virus-specific CD8(+) T cells. In this study, we examined the Vbeta diversity and avidity of CD8(+) T cells specific to the predominant epitope (VP2(121-130)) of Theiler's murine encephalomyelitis virus. We found that Vbeta6(+) CD8(+) T cells, associated with epitope specificity, predominantly expanded in the CNS during viral infection. Further investigations of antigen-specific Vbeta6(+) CD8(+) T cells by CDR3 spectratyping and sequencing indicated that distinct T-cell clonotypes are preferentially increased in the CNS compared to the periphery. Among the epitope-specific Vbeta6(+) CD8(+) T cells, MGX-Jbeta1.1 motif-bearing cells, which could be found at a high precursor frequency in naïve mice, were expanded in the CNS and tightly associated with gamma interferon production. These T cells displayed moderate avidity for the cognate epitope rather than the high avidity normally observed in memory/effector T cells. Therefore, our findings provide new insights into the CD8(+) T-cell repertoire during immune responses to viral infection in the CNS.
Kang
Hyun Seok
HS
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Kim
Byung S
BS
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018188:Cardiovirus Infections / Q000276:immunology*; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000821:virology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology / Q000821:virology; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*
D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta