T cells Flashcards
MHC Molecules
• Glycoproteins which are encoded by a set of closely linked genes in a region of the genome called the Major Histocompatibility (MHC) Complex (also known as HLA Complex)
- First identified by their effects in tissue transplantation
- When donor and recipient are of different MHC types then the recipient rejects
- Expressed on the surface of some cells where they display processed pep5des to T cells
- Two classes; MHC class I and MHC class II
- MHC class I expressed on ALL nucleated cells,
- Presents peptide from intracellular pathogens to CD8+ T cells
- MHC class II expressed on APCs, thymic epithelial, and activated T cells
- Presents peptide from extracellular pathogens to CD4+ T cells
Properties of MHC Molecules
MHC molecules are co-ordinately expressed • All class I or all class II molecules are expressed on a given cell surface simultaneously
MHC molecules are highly polymorphic
• Multiple alleles of each MHC gene exist in different individuals
MHC molecules are co-dominantly expressed
• Both maternal and paternal MHC genes are expressed in same
cell
MHC Haplotype
• Combination of HLA alleles on a given chromosome 6
Processing of Exogenous Antigens
Taken in and processed in phagolysosome
CLIP protein put in place because instability
cd74 –> CLIP
through golgi apparatus Clip becomes Invariant chain
MHC class II assembled with ii
ribosomes come and synthesis indivisual MHC class II alpha and beta chains
released on surface to CD4 t cells
Processing of Endogenous Antigens
Virus infection, goes into cell, the viral protein is an endogenous antigen
The MHC class I has Beta-2 microglobulin chain with Alpha 1, 2, 3
Tap 1 and Tap 2 preptide transporters bring proteins to it
released on surface to CD8 t cells
characteristics of T cells
- Express surface receptors known as T-cell receptors (TCRs) which recognize peptide presented by MHC (dual recognition)
- Respond to antigens that have invaded the cell
- When activated, naïveT-cells proliferate and differentiate into effector or memory cells
- Function of effector T-cells is determined by cell surface expression of CD4 or CD8 Co-receptor
- T cells expressing CD4 recognize class II MHC molecules plus peptide
- T cells expressing CD8 are cytotoxic & recognize class I MHC molecules plus peptide
- Activated T cells produce and secrete cytokines which act on the cells that secrete them or different cells
TCR COMPLEX
Consists of:
Antigen binding region–
Variable region is where antigen binds
V alpha and V beta
CD3 complex:
on t cell surface, helps with recognition
Epilson, delta, epsilon, gamma
Itams: Help send signal
CD4 and CD8 Co-receptors
Transmembrane molecules expressed on T-cells Must bind MHC molecule for effective T-cell response Mature T cells express either CD4 or CD8 (not both) CD4 binds MHC class II
CD8 binds MHC Class I
Noncovalently associated with TCR and co-operate with TCR in recognition of peptide + MHC
Lowers dose of Ag required for activation by 100 fold
Intracellular portion interacts with kinases in cytoplasm and transduces activating signal
Receptor-ligand interactions on T cells and APCs
T CELL + APC
CD28 + B7: COSIGNAL
(works along side CD3 for signal transduction)
CTLA 4 + B7: INHIBITORY
PD-1 + PD-1L: INHIBITORY (ITIM)
LFA-1 + ICAM: ADHESION
Autoimmune Polyendocrinopathy-candidiasis ectodermal dystrophy (APECED)
• Autoimmune disease characterized by hypo-parathyroidism, candidiasis, adrenal insufficiency, hypogonadism, type I diabetes
• Recessive mutant AIRE genes •
AIRE gene
• Transcription factor that allows tissue specific genes to be expressed by thymic epithelial cells
T cell Maturation and selection in the thymus
- Stem cell
- Double neg cell (PRO-T CELL)
- IL-7 induces proliferation
- Pre-TCR (b chain rearragement & association w/ pre-t-alpha
- Double positive (CD4+CD8+) immature t cell. functional alphabeta receptor
- negative selection
6a. Weak recognition of class II MHC + peptide –> positive selection for mature CD4 T cell
6b. Weak recognition of class I MHC + peptide –> positive selection for mature CD8 T cell
6c. NO recognition of class I or II MHC + peptide –> failure of positive selection, death by neglect
6d. STRONG recognition of class I or II MHC + peptide –> negative selection
Positive Selection
by cortical epithelial cells in the thymus cortex
- Double positive (CD4+CD8+) immature t cell. functional alphabeta receptor
Negative selection
of alpha-beta t cells by dendritic cells, macrophages, and other cells in the thymus medulla
6a. Weak recognition of class II MHC + peptide –> positive selection for mature CD4 T cell
6b. Weak recognition of class I MHC + peptide –> positive selection for mature CD8 T cell
6c. NO recognition of class I or II MHC + peptide –> failure of positive selection, death by neglect
6d. STRONG recognition of class I or II MHC + peptide –> negative selection
T Cell Dependent (TD) B cell Activation
cognate interaction with T cell required
- For a B cell to be activated by a protein antigen, it requires 2 signals
- Antigen provides signal 1
- T cell help provides signal 2
- Interaction with T cell co-stimulatory molecule, CD40L needed for 2nd signal
- T cell cytokines enhance 2nd signal
T independent response (TI)
Do not require T cell help to activate B cells
TI-1 response
• B cells activated by combination of signals through BCR
and TLR
TI-2 response
• Large polymeric molecules with repeating identical
polysaccharide subunits
• Activate B cells by extensively crosslinking mIg • Activate only mature B cells
Map Kinase Cascade RAS/RAC
AP-1 increased
