CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection but Also During Peripheral T-Dependent Humoral Immune Responses

Anke Faehnrich (1) , Sebastian Klein (1) , Arnauld Serge (2) , Christin Nyhoegen (1) , Sabrina Kombrink (1) , Steffen Moeller (3) , Karsten Keller (1) , Juergen Westermann (1) , Kathrin Kalies (1)

1 University of Luebeck
2 CRCM - Centre de Recherche en Cancérologie de Marseille
3 Institute for Biostatistics and Informatics in Medicine and Ageing Research

CD154 is a transmembrane cytokine expressed transiently on activated CD4 T cells upon T-cell receptor (TCR) stimulation that interacts with CD40 on antigen-presenting cells. The signaling via CD154:CD40 is essential for B-cell maturation and germinal center formation and also for the final differentiation of CD4 T cells during T-dependent humoral immune responses Recent data demonstrate that CD154 is critically involved in the selection of T-cell clones during the negative selection process in the thymus. Whether CD154 signaling influences the TCR repertoire during peripheral T-dependent humoral immune responses has not yet been elucidated To find out, we used CD154-deficient mice and assessed the global TCR beta repertoire in T-cell zones (TCZ) of spleens by high-throughput sequencing after induction of a Th2 response to the multiepitopic antigen sheep red blood cells Qualitative and quantitative comparison of the splenic TCZ-specific TCR beta repertoires revealed that CD154 deficiency shifts the distribution of V beta-J beta genes after antigen exposure. This data led to the conclusion that costimulation via CD154:CD40 during the interaction of T cells with CD40-matured B cells contributes to the recruitment of T-cell clones into the immune response and thereby shapes the peripheral TCR repertoire.

Domaines: Sciences du Vivant [q-bio]

Anke Faehnrich, Sebastian Klein, Arnauld Serge, Christin Nyhoegen, Sabrina Kombrink, et al.. CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection but Also During Peripheral T-Dependent Humoral Immune Responses. Frontiers in Immunology, 2018, 9, ⟨10.3389/fimmu.2018.01019⟩. ⟨hal-02143668⟩