Lecture 6: MHC and Ag Presentation to T cells Flashcards
in order to activate T cells Antigens in host cells are broken up into ____ peptides (processed) and displayed by MHC molecules on their surface
linear
T T cell antigen receptor (TCR) only recognizes ____ Antigens (peptides) bound to MHC molecules
linear peptides (processed)
CD4 and CD8 attach to the _____ part of the MHC class II and MHC class I molecules, respectively
non-polymorphic (non-variant)
is recognition of the peptide Ag by the TCR sufficient to activate the naive T cells
- No: co-stimulatory molecules are required together with co-receptors
Th1 cells help ___ to get rid of intracellular microbes and help the development of ______ to kill virus-infected cells
- Macrophages, CTLs
Th2 cells are mainly involved in helping _____ cells develop into ____ and ____
B cells develop into memory cells and plasma cells that produce antibodies
The TCR is composed of _______ polypeptide chains
two (most are alpha and beta but some are are gamma and delta chains)
The gamma/delta T cells have some of the characteristics of alpha/beta T cells, but have a
broader specificity for unconventional Ag such as HSPs and phospholipids
The genes coding for TCR polypeptide chains are members of the
Ig super family
The T cell receptor complex consists of the TCR, the alpha/beta or gamma/delta dimer, in association with
CD3
CD3 is a signaling complex composed of ___, ____ and ____ chains
gamma, delta, and epsilon
What are the three major class genes for Class I MHC
- HLA-A
- HLA-C
- HLA-B
- on chromosome 6
What genes are responsible for MHC class II
- HLA-DR
- HLA-DQ
- HLA-DP
- on chromosome 6
Class I MHC genes (HLA-A, HLA-B, and HLA-C) encode a polymorphic heavy chain which combines with _____ and is expressed on the surfaces of all nucleated cells
beta2-microglobulin
Class II MHC genes (HLA-D) encode molecules (HLA-DP, HLA-DR, HLA-DQ) composed of two dissimilar ____________ (an alpha and beta chain), both of which contribute to the peptide-binding groove
polymorphic polypeptide chains
MHC class I and class II are the peptide-binding domains of these molecules and bind peptides ranging from _____ and _____ amino acids residues, respectively
8-10 (MHC class I)
10-20 (MHC class II)
Class I molecules are composed of a polymorphic alpha chain non-covalently attached to the ___________
non-polymorphic Beta2-microglobulin (beta2m)
class II MHC molecules are composed of a polymorphic alpha chain non-covalently attached to a
polymorphic beta chain
source of protein antigens for Class II MHC molecules
Endosomal/lysosomal proteins (mostly internalized from extracellular environment)
Source of protein antigens for class I MHC molecules
Cytosolic proteins (mostly synthesized in the cell; may enter cytosol from phagosomes)
Site of peptide loading for MHC class II
Specialized vesicles
Site of peptide loading of MHC class I
Endoplasmic reticulum
enzymes responsible for pepide generation for MHC class II
Endosomal and lysosomal proteases (e.g. cathepsins)
Enzymes responsible for peptide generation for MHC class I
Cyoplasmic proteasome
Molecules involved in transport of peptides and loading of MHC class II molceules
Invariant chain, DM
Molecules involved in transport of peptide and loading of MHC class I molecules
TAP
Peptide Ags that bind to class II MHC complexes are from the ____ pathway while peptide antigens for class I MHC are taken from the ____ pathway
- exogneous pathway (MHC class II)
- endogenous pathway (MHC class I)
what is CLIP
- Class II-associated invariant chain peptide
- it 24-amino acid remnant of the invariant chain that is placed in the peptide binding site. it is removed by HLA-DM (HLA-DM is a peptide exchanger that removes the CLIP and allows for the addition of other peptides)
MHC class II (along with the invariant chain) is formed in the
ER
What are the 3 major functions of HLA-DM
- HLA-DM causes the dissociation of CLIP from the peptide binding groove of MHC II
- HLA-DM stabilizes and prevents degradation of the empty MHC II
- HLA-DM facilitates the binding of Ag fragments to the open, stabilized binding groove
How is CLIP formed
the degradation of the invariant chain by proteolytic enzymes in the endosome. This forms the 24 amino acid invariant chain known as CLIP
What are immunodominant peptides
Applies to peptides presented by both class I and class II MHC molecules
