Advanced Course in Immunology On Demand Lecture Recordings-Antigen Receptor Signaling

Video Transcription

Video Summary

The lecture provided a broad overview of antigen receptor signaling, with a major focus on T-cell receptor (TCR) signaling and how it drives T-cell activation, differentiation, and immune responses. The speaker emphasized the importance of spatial organization, since T cells recognize antigen only when peptide-MHC is presented on another cell, requiring close cell-cell contact and formation of signaling microclusters and the immune synapse.<br /><br />Key early signaling events include phosphorylation of ITAM motifs on CD3 and zeta chains by the Src-family kinase LCK, followed by recruitment and activation of ZAP70. The talk described regulation of these kinases by CD45, CSK, lipid raft localization, and conformational control. LAT was highlighted as a central adaptor that assembles a “signalosome,” recruiting proteins such as GADS, SLP76, PLC-gamma1, and others to propagate signals.<br /><br />Downstream pathways included calcium signaling and calcineurin-dependent activation of NFAT, Ras/MAPK signaling leading to AP1, and PI3 kinase pathways activated in part by CD28 costimulation. The lecture also covered actin remodeling, integrin activation, and the graded nature of T-cell responses. Negative regulation via ubiquitination, phosphatases, receptor internalization, and checkpoint receptors such as CTLA-4, PD-1, and LAG-3 was discussed.<br /><br />Finally, the speaker connected these pathways to disease and therapy, including immunodeficiency, lymphoma, checkpoint blockade, and CAR-T cell engineering.

Asset Subtitle

Lecture 11: Lawrence P. Kane, University of Pittsburgh

Antigen Receptor Signaling

Asset Caption

Lawrence P. Kane, University of Pittsburgh
Antigen Receptor Signaling

Keywords

T-cell receptor signaling

antigen receptor

immune synapse

LCK kinase

ZAP70

LAT signalosome

CD28 costimulation

NFAT activation

Ras/MAPK pathway

actin remodeling

checkpoint receptors

CTLA-4 PD-1 LAG-3

CAR-T therapy