An invariant VLR-like receptor refines the T-like cell framework in lamprey.

Area of Science:

• Immunology
• Evolutionary Biology
• Genomics

Background:

• Jawless vertebrates, like lampreys, possess a unique adaptive immune system utilizing variable lymphocyte receptors (VLRs).
• The cellular organization and diversity of VLR expression within individual lymphocytes remain incompletely understood.
• Previous studies identified multiple VLRs and T/B-like lymphocytes in lampreys.

Purpose of the Study:

• To investigate the cellular organization of VLR diversity in lamprey lymphocytes.
• To identify and characterize novel VLRs and their associated cell populations.
• To explore the potential for individual lymphocytes to express multiple VLRs.

Main Methods:

• Single-cell transcriptomics was employed to analyze lymphocyte populations.
• A monoclonal antibody against the VLR-like receptor was generated.
• Lymphocyte activation and function were assessed via stimulation and functional assays.

Main Results:

• A novel, germline-encoded, non-diversified VLR-like receptor was identified on T-like cells in lamprey Lethenteron reissneri.
• VLR-like+ lymphocytes exhibited T-cell characteristics, including ERK/JNK phosphorylation and proliferation, but lacked B-cell functions.
• VLR-like+ cells were distinct from VLRA+ lymphocytes and showed heterogeneous co-expression of VLRC, interacting with VLRC but not VLRA.

Conclusions:

• VLR-like defines a distinct T-like lymphocyte population in lampreys.
• This population exhibits heterogeneous co-expression of VLRC.
• A model is proposed where invariant VLR-like coordinates diversified VLRs within a single T-like cell, contributing to adaptive immunity.