Predominant Clonal Accumulation of CD8⁺T Cells with Moderate Avidity in the Central Nervous Systems of Theiler's Virus-Infected C57BL/6 Mice

Abstract

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 V␤ diversity and avidity of CD8 ؉ T cells specific to the predominant epitope (VP2 121-130 ) of Theiler's murine encephalomyelitis virus. We found that V␤6 ؉ CD8 ؉ T cells, associated with epitope specificity, predominantly expanded in the CNS during viral infection. Further investigations of antigen-specific V␤6 ؉ 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 V␤6 ؉ CD8 ؉ T cells, MGX-J␤1.1 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.

Antigen-Specificity of T Cell Infiltrates in Biopsies With T Cell–Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing

“…In one study, circulating alloreactive T cells correlated with graft function in longstanding renal transplant recipients . However, it is also known that T cell clonal frequencies in the peripheral blood can differ substantially from those in specific organs . Clonal amplification thresholds corresponding to specific biopsy diagnoses such as TCMR or BKPyVN will have to be established in a prospective clinical trial.…”

Clonal Expansions of CD8+ T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection

“…Clonal CD8 + expansions have been described in TB patients [52], including pediatric TB [42], supporting the relevance of our findings to TB in man. Clonal CD8 + expansions are also common in the elderly and in many viral models [42,43,[53][54][55][56][57][58], yet their importance in Mtb infection is still unclear.…”

The Level of Viral Infection of Antigen-Presenting Cells Correlates with the Level of Development of Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease

“…Infection of resistant mice with TMEV is successfully cleared in mice with strong early phase protective T cell responses, in contrast to susceptible mice displaying weak early phase immune responses. As a consequence, viral persistence in susceptible mice eventually leads to the development of chronic demyelinating disease (35). Levels and/or qualities of T cell immune responses are associated with the development of TMEV-induced demyelinating disease (15).…”