Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck

• Published in: Frontiers in immunology 2021-10, Vol.12, p.721722-721722
• Main Authors: Zhao, Xiang, Wu, Liang-Zhe, Ng, Esther K Y, Leow, Kerisa W S, Wei, Qianru, Gascoigne, Nicholas R J, Brzostek, Joanna
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; co-agonism; Cytokines - genetics; Cytokines - metabolism; Gene Expression Regulation; Histocompatibility Antigens Class I - immunology; Host-Pathogen Interactions; Immunological Synapses - metabolism; Immunology; Lck; Lymphocyte Activation - immunology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism; Mice; non-stimulatory peptide MHC; Phosphorylation; Protein Binding; Protein Transport; Quorum Sensing; T cell effector functions; T cell receptor; T cell signaling; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.721722

Under physiological conditions, CD8 T cells need to recognize low numbers of antigenic pMHC class I complexes in the presence of a surplus of non-stimulatory, self pMHC class I on the surface of the APC. Non-stimulatory pMHC have been shown to enhance CD8 T cell responses to low amounts of antigenic pMHC, in a phenomenon called co-agonism, but the physiological significance and molecular mechanism of this phenomenon are still poorly understood. Our data show that co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8 T cell signaling pathways, resulting in enhanced CD8 T cell effector functions and proliferation, both and . Moreover, co-agonism can boost T cell proliferation through an extrinsic mechanism, with co-agonism primed CD8 T cells enhancing Akt pathway activation and proliferation in neighboring CD8 T cells primed with low amounts of antigen.