MHC Flashcards
Role of MHC / HLA molecules:
- main role
is during Antigen Presentation to T cells
- play a pivotal role in development of both humoral and cellular immunity
MHC/ HLA
MHC/ HLA
- during transplants:
used to determine whether a transplanted or to be transplanted tissue is:
- histocompatible and thus accepted
- recognized as foreign and rejected
MHC/ HLA
- may be involved during:
- Graft Rejections
- Autoimmune Diseases
- Paternity Tests
- Transfusion Reactions
Why are MHC/ HLA Gene System
- Polymorphic:
there are so many possible alleles at each location to increase chances of interacting with diverse self and non-self antigens/immunogens
MHC/ HLA
Coded in the…
Except…
short arm of chromosome 6 band 21 (6p21)
Beta-2 in chromosome 15
MHC/ HLA gene system
Divided into 3 categories (classes)
- Class I
- Class Il
- Class III
MHC
Class I
ABC
MHC CLASS II
D:PQR
MHC CLASS III
Complement proteins
Cytokines
Tumor necrosis factor
Expressed on cell surface
MHC CLASS I and CLASS II
MHC Class I
(HLA-A, HLA-B, HLA-C)
MHC Class I
(HLA-A, HLA-B, HLA-C)
MHC Class | (HLA-A, HLA-B, HLA-C)
• expressed by…
• highly found on…
• Low or undetectable on… (4)
ALL nucleated cells
Lymphocytes & Myeloid Cells
hepatocytes, muscle cells, sperm cells, neural cells
What MHC/ HLA
IS expressed the lowest
HLA-C
What MHC/ HLA
(______ and ______ are more important!)
HLA-A and HLA-B
Structure of MHC Class I
glycoprotein dimer:
2 non-covalently bonded polypeptide chains: - Alpha - Beta
Structure of MHC class I
ALPHA chains
- MW: ____
- folded into 3 domains:
-_______ anchored to the cell membrane
44,000
- Alpha 1
- Alpha 2
- Alpha 3
polypeptide chain
Structure of MHC Class I
BETA chain
- MW:_____
- coded on______
- Beta…
- stabilize folded____
- not polymorphic: why?..
12,000
chromosome15
B2 microglobulin
alpha chain
every class I molecule contains the same B2 microglobulin
MHC Class III
HLA proteins
BF, C2, C4, TNF
MHC CLASS I
MHC CLASS II
Chain Structure
3 alpha, 1 beta2-microglobulin
2 alpha and 2 beta
MHC CLASS I
MHC CLASS II
MHC CLASS III
Found on
All nucleated cells
APCS
Blood and other secretions
MHC CLASS I
MHC CLASS II
Example of infectious agent
Viruses, Tumor, Certain Parasitic Antigens, Intracellular bacteria
Bacteria
MHC CLASS I
MHC CLASS II
MHC CLASS III
Antigen Presentation
CD8+
CD4+
No role in antigen presentation
- molecular basis for T-cell discrimination of self from non-self
Human Leukocyte Antigens
HLA
- Name was given by…
- discovery of antibody response to…
French Scientist (Jean Dausset)
circulating WBCs
- determine whether transplanted tissue is histocompatible and thus accepted or recognized as foreign and rejected
- Antigen presentation
Major Histocompatibility Complex
- in general: Gene system which plays a key immunologic role.
MHC
Structure of MHC Class I
ALPHA 1 and 2
- serves as…
- able to hold…
antigen binding site
8 - 11 amino acids
Structure of MHC Class I
ALPHA 3
- detected by…
CD8 on Cytotoxic cells
MHC CLASS I NONCLASSICAL GENE
EFG
Nonclassical antigens
Expression
E - cell surface
F - cell surface
G - nit expressed on cell surface
Nonclassical antigens
Function
E - expressed on fetal trophoblast cells during first trimester of pregnancy protection of placental tissue from NK
cells
F - Unknown
G - expressed on fetal trophoblast cells during first trimester of pregnancy protection of placental tissue from NK
cells
MHC Class II (HLA-DP, HLA-DQ, HLA-DR)
•expressed by____
•_______: highest expression
APCs
Dendritic cells
MHC Class II (HLA-DP, HLA-DQ, HLA-DR)
: lowest
:is expressed at the highest level
HLA-DP
HLA-DR
MHC Class II (HLA-DP, HLA-DQ, HLA-DR)
is expressed at the highest level accounts for about ½ of Class Il molecules of a particular cell
HLA DR
MHC Class II (HLA-DP, HLA-DQ, HLA-DR)
: the most highly polymorphic
HLA-DR Beta
Structure of MHC Class II
- Consist of…
- ALPHA
- BETA
- _______anchored in the cell membrane
two noncovalently bonded polypeptide chains, both of which is encoded at the chromosome 6
Both chains are
Structure of MHC Class II
ALPHA chains
- MW:
- folded into 2 domains:
- both:
34,000
- ALPHA 1
- ALPHA 2
serves to as recognition sites by T helper cells via the CD4 surface marker
Structure of MHC Class II
ALPHA 1 and BETA 1 domains
- can hold up to…
- antigen-peptide-binding site
13 - 18 aa
MHC Class II: Nonclassical
Function
DM
DN
DO
Loads peptides onto class Il
Unknown
Modulates antigen binding