Lecture 7: MHC and Antigen Presentation to T Cells Flashcards
Cell mediated immunity is due to
The direct action of T cells
T cells also HELP with
HELP mount a robust Ab-mediated humoral immune response directed against extracellular pathogens
TCR
T cell antigen receptor
Glycoprotein
Only recognizes peptides bound to MHC molecules
Each T cell recognizes
Only one specific foreign peptide
CD4+ T helper cells recognize
Peptide Ags in the context of MHC class II molecules that are expressed by DCs, macrophages and B cells
CD8+ cytotoxic T cells recognize
Peptides associated with MHC class I molecules
Differential requirement for CD4 and CD8 in the context of MHCs relates to
The fact that CD4 and CD* attach to the non-variable part of the MHC class II and I molecules, respectively
Does recognition of the peptide Ag by the TCR activate T cells?
No, this is not sufficient. There must also be co-stimulatory molecules expressed by APCs
T-cell activation leads to production of
IL-2, which controls clonal expansion of the specific T cells
Th1
Helper T cell
Activated Th1 produce IFN-y which activate macrophages and help development of cytotoxic T cells to kill virus infected cells
(intracellular microbes)
Th2
Helper T cell
Help B cells develop into memory cells and plasma cells that produce antibodies
Produce IL-4, important for B cell proliferation
(extracellular microbes)
a/b T cells vs yd T cells
ab T cells are conventional T cells
yd T cells have some characteristics of ab T cells but have broader specificity for unconventional Ags such as HSP and phospholipids
TCR associates with what
CD3, a signaling complex
MHC class II expressed on
Only on professional Antigen Presenting Cells APCs
DCs, macrophages, B cells
MHC class I expressed on
All nucleated cells in the body
Two classes of MHC genes encode
Human leukocyte antigen HLA that can bind peptides and are thus critical to Ag presentation
Polymorphic regions of MHC class I and II
Peptide binding domains
MHC I- binds peptides 8-10 AAs long
MHC II- binds peptides 10-20 AAs long
Class I molecules composed of
Polymorphic a-chain, non-covalently attached to the non-polymorphic B2-microglobulin
alpha-chain is glycosylated
Class II molecules composed of
Polymorphic a-chain non-covalently attached to polymorphic B chain
Both chains are glycosylated
Anchor residue
Residues on peptides that bind to residues in class I and II grooves and vary for different MHC alleles
Co-dominant expression of MHC
Both parental alleles of each MHC gene are expressed, increasing number of different MHC molecules that can present peptides to T cells
Polymorphic genes and MHC
Ensures that different individuals are able to present and respond to different microbial peptides
Peptides that bind to MHC class I are derived from
Viruses and other intracellular microbes that have infected host cells
(endogenous pathway)
Peptides binding to MHC class II are derived from
Mostly Ags and extracellular pathogens taken from the environment
Dendritic cell class II expression
Constitutive, increases with maturation
Increased by IFN-y
Dendritic cell principal function
Initiation of T cell responses to protein antigens
Macrophage Class II expression
Low or negative, inducible by IFN-y
Macrophage principal function
Effector phase of cell-mediated immune responses
B lymphocytes class II expression
Constitutive, increased by IL-4
B lymphocyte principal function
Ag presentation to CD4+ helper T cells in humoral immune response
CD40 and CD40L
CD40 is a costimulatory protein found on professional APCs and is required for their activation. The binding of CD40L on T cells to CD40 activates the APC
Microbial Ags entering through skin, GI and respiratory tracts are responded to by
Dendritic cells and transported to lymph nodes
Ags entering the blood stream are captured by
APCs in the spleen
Tissue resident DC expression Vs activated DC expression
Tissue resident DCs express mannose and Fc receptors
Activated DCs express molecules involved in T cell activation (B7, ICAM-1, IL-12)
NK cells and T cells produce
IFN-y, which stimulates class II MHC expression on APCs and thus enhances the activation of CD4+ T cells (IFN-y and type I interferons have similar effect on expression of MHC class I molecules and activation of CD8+ T cells)
a/b T cells recognize
Linear peptides
Cell-associated, non-soluble Ags
CD4+ T cells recognize
Extracellular Ags because MHC II molecules display peptides that are taken up from the extracellular environment of APCs by pino/phagocytosis
CD8+ T cells recognize
Intracellular Ags because MHC I molecules present peptides from cytosolic proteins including intracellular pathogens
CLIP
Class II associated invariant chain peptide -There are a lot of self peptides in the ER which are prevented from binding to class II MHC by the invariant chain
HLA-DM
Causes dissociation of CLIP from peptide binding groove of MHC II
Stabilizes and prevents degradation of the empty MHC II
Facilitates the binding of Ag fragments to the open, stabilized binding groove
TAP
Transporter associated with Ag processing
Transports processed cytosolic peptides into the ER to be matched with MHC I molecule
How do DCs present Ags for CD8+ T cells
Fragments of cells infected with intracellular microbes are ingested by DCs Ags are transported into cytosol and presented in association with class I MHC molecules to CD8 T cells Thus, DCs are able to present extracellular Ags by the class I pathway
Immunodominant peptides
Processing generates multiple different peptides
Immunodominant peptide is the best fit
