MHC Flashcards
What is the Major Histocompatability Complex?
• a large cluster of genes encoding specialized glycoproteins; many functions
What is the most important role of MHC?
•• role in antigen presentation to T cells ••
T/F T cells ONLY recognize peptides bound to MHC molecules
true
Of the MHC I characteristics, which is the same throughout all individuals
B2- microglobulin
Describe peptide binding of MHC
- each MHC molecule (class I or class II) can bind to many different peptides
- MHC class I and class II molecules do have slightly different peptide-binding characteristics
Describe the binding cleft of MHC class I molecules
is closed
Compared to MHC I, the ability of MHC II to bind to peptides is what?
less restrictive
the binding cleft of MHC class I molecules is closed and will only bind to peptides with what length of AA?
between 8-10 amino acids in length
Peptide binding to MHC I is stabilized how?
stabilized by contacts between the aminoterminal and carboxyterminal ends of the peptide and invariant sites found at the ends of the binding grooves
Describe the binding cleft of MHC II
the binding cleft of MHC class II molecules is open;
the ends of the peptide can hang over the edge of the cleft
MHC II will bind peptides of what length?
will bind to peptides at least 13 amino acids in length, and can be much longer
How is MHC II stabilized?
peptide binding is stabilized by contacts between the peptide backbone and conserved residues that line the MHC class II binding groove
MHC Class I Ag-Processing and Presentation Pathway (4 steps)
- class I HC is stabilized by calnexin until B2-microglobulin binds
- calnexin released and heterodimer of class I HC and B2-mg forms peptide-loading complex with clareticulin, tapasin, TAP, ERp57, and PDI
- peptide delivered by TAP binds to class I HC, forming mature MHC I molecule
- class I molecule dissociates from the peptide-loading complex, and is exported from the ER
What is step 1 of MHC Class I Ag-Processing and Presentation Pathway?
class I HC is stabilized by calnexin until B2-microglobulin binds
What is step 2 of MHC Class I Ag-Processing and Presentation Pathway?
calnexin released and heterodimer of class I HC and B2-mg forms peptide-loading complex with clareticulin, tapasin, TAP, ERp57, and PDI
What is step 3 of MHC Class I Ag-Processing and Presentation Pathway?
peptide delivered by TAP binds to class I HC, forming mature MHC I molecule
What is step 4 of MHC Class I Ag-Processing and Presentation Pathway?
class I molecule dissociates from the peptide-loading complex, and is exported from the ER
Describe the antigen presentation to T cells wrt to MHC I
- intracellular antigen processing to peptides in proteasome
- peptide transport into ER
- peptide binding by MHC I
- MHC I presents peptide at cell surface
Describe the MHC Class II Ag-Processing and Presentation Pathway (4 steps)
- invariant chain blocks binding of peptides to MHC II molecules in ER
- in vesicles invariant chain is cleaved, leaving the CLIP fragment bound
- CLIP blocks binding of peptides to MHC II in vesicles
- HLA-DM facilitates release of CLIP, allowing peptides to bind
What is step 1 of MHC Class II Ag-Processing and Presentation Pathway?
invariant chain blocks binding of peptides to MHC II molecules in ER
What is step 2 of MHC Class II Ag-Processing and Presentation Pathway?
in vesicles invariant chain is cleaved, leaving the CLIP fragment bound
What is step 3 of MHC Class II Ag-Processing and Presentation Pathway?
CLIP blocks binding of peptides to MHC II in vesicles
What is step 4 of MHC Class II Ag-Processing and Presentation Pathway?
HLA-DM facilitates release of CLIP, allowing peptides to bind
describe Antigen Presentation to T Cells wrt to MHC class II
- extracellular antigen endocytosed
- peptide production in phagolysosome
- peptide binding by MHC II
- MHC II presents peptide at cell surface
Describe how MHC molecules present peptides to T cells
CD4 T cells recognize peptides bound to MHC class II
CD8 T cells recognize peptides bound to MHC class I
What is the Significance of MHC Distribution? (2)
- MHC molecules present peptides to T cells
- immune response is “tailored” to the type of infection
Describe how immune response is “tailored” to the type of infection
Ab-mediated immune responses best for clearance of extracellular pathogens
T cell-mediated immune responses are best for clearance of intracellular pathogens
What is the existence in the genome of several different genetic loci encoding structurally similar proteins of identical function (isoforms)?
polygeny
What is the existence of two or more forms (alleles) of a given gene within the population (variant alleles occur at a frequency of at least 1%)?
Polymorphism (genetic)
Describe the genes MHC I inherited
3 MHC class I gene on each chromosome
- HLA-A
- HLA-B
- HLA-C
Describe the genes MHC II inherited
each person inherits at least 3 MHC class II genes on each chromosome
- HLA-DP
- HLA-DQ
- HLA-DR (either 1 or 2 on each chromosome)
T/F MHC expression is what?
polygenic
Describe the minimum number of MHC molecules expressed/person (both classes)
3 different MHC class I molecules
3 different MHC class II molecules
What is • maximum number of MHC molecules expressed/person? (both classes)
6 different MHC class I molecules
48 different MHC class II molecules
any tissue bearing non-self MHC will be rejected. Why?
T cell-mediated immune response
MHC in Transplant Rejection
What is a transplant between genetically identical individuals?
syngeneic transplant (isograft)
What is a transplant between genetically different individuals?
allogeneic transplant (allograft)
What is a transplant of tissue from a different species?
zenograft
Describe what is necessary before a bone marrow transplant and what occurs after
bone marrow transplant: host immune system is destroyed prior to transplant
following transplant, mature T cells (from transplant) attack allogeneic tissue of the host
