TCR-signals downstream adversely correlate with the survival signals of memory CD8+ T cells under homeostasis

Abstract

The significance of self-peptide-MHC-I/TCR (SMT) interaction in the survival of CD8⁺ T cells during naïve- and developmental-stages is well documented. However, the same for the memory stage is contentious. Previous studies have attempted to address the issue using MHC-I or TCR deficient systems, but inconsistent findings with memory CD8⁺ T cells of different TCR specificities have complicated the interpretation. Differential presence and/or processing of TCR-signals downstream in memory CD8⁺ T cells of different TCR specificities could be thought of as a reason. In this study, we examined the TCR-signals downstream in memory CD8⁺ T cells and compared them to the presence of survival-related signals (Annexin-V, Bcl-2, and Ki-67). We categorically tracked foreign antigen-experienced memory CD8⁺ T (TM) cells generated after Plasmodium pre-erythrocytic-stage malaria infection in C57BL/6 mice. Interestingly, we found that memory CD8⁺ T cells had more TCR-signals downstream than naive cells. We reasoned and attributed the increased expression of cell adhesion molecules to the enhanced TCR-signaling. TCR-signals downstream correlate more closely with survival signals in naive CD8⁺ T cells than with death signals in TM cells. Further investigation using antigen-specific CD8⁺ T cells and diverse infection systems would aid in conceptualizing the findings.

Keywords: Annexin-V; Bcl-2; Ki-67; Memory CD8(+) T cell; Nur77; Self-peptide-MHC-I/TCR interaction; TCR signal.