4.3 Antigen presentation to T cells

T cells are the immune system's precision weapons, recognizing specific threats through MHC-peptide complexes. This interaction triggers a cascade of events, from T cell activation to differentiation, shaping our body's defense strategy.

Understanding how T cells respond to antigens is crucial for grasping immune function. CD4+ and CD8+ T cells have distinct roles, recognizing different types of threats and coordinating varied immune responses to keep us healthy.

MHC-Peptide Complexes and T Cell Activation

MHC-peptide and T cell receptor interaction

• MHC-peptide complex structure forms antigen presentation platform
  • MHC Class I α chain and β2-microglobulin present intracellular peptides
  • MHC Class II α and β chains present extracellular peptides
• T cell receptor (TCR) structure recognizes specific peptide-MHC combinations
  • α and β chains form antigen-binding site
  • CD3 complex transduces activation signals
• Binding mechanism involves molecular recognition and conformational changes
  • Complementarity-determining regions (CDRs) of TCR contact peptide and MHC
  • Peptide-binding groove of MHC molecules accommodates diverse peptides
• Specificity and affinity determine T cell activation threshold
  • Clonal selection theory explains unique TCR specificity (one clone, one specificity)
  • Positive and negative selection in thymus shapes T cell repertoire
• Co-receptors enhance TCR-MHC interaction and signaling
  • CD4 binds MHC Class II (helper T cells)
  • CD8 binds MHC Class I (cytotoxic T cells)

Co-stimulatory molecules in T cell activation

• Two-signal model of T cell activation prevents inappropriate responses
  • Signal 1 TCR-MHC-peptide interaction provides specificity
  • Signal 2 Co-stimulatory molecules amplify and sustain activation
• B7 family of co-stimulatory molecules on antigen-presenting cells
  • B7-1 (CD80) and B7-2 (CD86) engage T cell receptors
• CD28 on T cells initiates co-stimulatory cascade
  • Binding to B7 molecules triggers intracellular signaling
  • Amplification of TCR signaling enhances T cell activation
• Consequences of co-stimulation boost immune response
  • IL-2 production drives T cell proliferation
  • T cell proliferation expands antigen-specific clones
  • Prevention of anergy ensures functional T cell responses
• Other co-stimulatory pairs fine-tune T cell responses
  • CD40-CD40L promotes B cell help and APC activation
  • ICOS-ICOSL supports T cell-dependent B cell responses

T Cell Responses and Differentiation

Consequences of antigen presentation

• T cell activation triggers complex signaling network
  • Intracellular signaling cascades (MAP kinases, calcium flux)
  • Transcription factor activation (NFAT, AP-1, NF-κB) drives gene expression
• T cell differentiation shapes immune response
  • CD4+ T cell subsets Th1, Th2, Th17, Treg tailor response to pathogens
  • CD8+ T cell differentiation into cytotoxic T lymphocytes (CTLs) targets infected cells
• Cytokine production orchestrates immune responses
  • IL-2 promotes T cell proliferation and survival
  • Subset-specific cytokines (IFN-γ, IL-4, IL-17) direct immune response
• Effector functions eliminate pathogens and infected cells
  • CD4+ T cells provide helper functions and cytokine production
  • CD8+ T cells perform cytotoxicity via perforin and granzyme release
• Memory T cell formation ensures long-term protection
  • Central memory T cells circulate in lymphoid organs
  • Effector memory T cells patrol peripheral tissues

CD4+ vs CD8+ T cell antigen requirements

• MHC restriction determines T cell subset activation
  • CD4+ T cells recognize peptides on MHC Class II
  • CD8+ T cells recognize peptides on MHC Class I
• Antigen source influences processing and presentation
  • CD4+ T cells respond to exogenous antigens (bacteria, toxins)
  • CD8+ T cells respond to endogenous antigens (viruses, tumors)
• Antigen-presenting cells vary in presentation capacity
  • CD4+ T cells activated by professional APCs (dendritic cells, macrophages, B cells)
  • CD8+ T cells can be activated by any nucleated cell presenting endogenous antigens
• Antigen processing pathways differ between MHC classes
  • CD4+ T cells endosomal/lysosomal pathway processes extracellular proteins
  • CD8+ T cells cytosolic pathway and proteasomal degradation process intracellular proteins
• Co-receptor involvement enhances TCR-MHC interaction
  • CD4+ T cells use CD4 co-receptor to stabilize MHC II binding
  • CD8+ T cells use CD8 co-receptor to stabilize MHC I binding
• Functional outcomes address different aspects of immunity
  • CD4+ T cells coordinate immune responses through helper functions
  • CD8+ T cells directly eliminate infected or malignant cells