Major Histocompatibility Complex (MHC)

MHC stands for Major ___ complex and is sometimes called HLA, ___ ___ ___.

Histocompatibility; Human Leukocyte Antigen

MHC is involved in the genetic ___ to mount immune response. It is found on all ___ cells (extremely polymorphic system).

capability; nucleated

MHC functions to bring small ___ antigen to the cell surface to be recognized by ___ cells. This will result in T cell activation and an immune ___!

peptide; T; response

Without MHC and the antigen being ___ down into small peptide to be shown to T cell - T cell ___ respond or do anything!

broken; cannot

MHC/HLA is clinically involved in transfusion reactions, ___ rejection, and ___ diseases!

graft; autoimmune

Having one autoimmune disease puts you at higher ___ of having a second one!

Ex. HLA marker associated w/ type 1 diabetes also associated with celiac disease.

risk

MHC is located on the ___ arm of chromosome ___, is closely linked and inherited together as a ___ (packaged deal).

short; 6; haplotype

There are ___ classes of MHC. Name all 3:

3; I, II, III

MHCI are found on ___ nucleated cells with levels varying between cell types (Lymphs = ___ concentration; Hepatocytes = ___ concentration).

all; high; low

MHCII are found on ___ ___ cells.

antigen presenting

Name the Antigen Presenting Cells:

B Cells, Monocytes and Macrophages, and Dendritic Cells

MHCIII are ___ found on cells, but ___. Found on certain ___ proteins and some cytokines.

not; secreted; complement

MCHI has ___ different loci (specific gene locations in chromosome 6) regions: ___, ___, and ___.

3; A; B; C

MHCII includes the ___ loci region: ___, ___, ___. (Doctor-Dairy Queen-Doctor Pepper)

It also includes alpha and beta ___.

D; DR; DQ; DP; chains

MHCIII code for ___ and ___.

complement; cytokines

We inherit one chromosome ___ copy from each parent.

6

Because HLA inheritance is ___, the HLA alleles inherited from both mom and dad are expressed.

codominant

Codominant inheritance of HLA alleles leads to the possibility of ___ alleles (polymorphic) at each loci (two copies of A, B, C, DP, DQ... etc).

This results in a huge amount of ___. With >1.7 billion combinations and person to person variation - it makes successful ___ difficult.

multiple; variation; transplants

A group of HLA alleles inherited together from one parent is called a ___. One HLA haplotype comes from each ___.

Ex. one copy for A with one copy for B and one copy for C come together.

haplotype; parent

Because we inherit a haplotype from both parents, we have ___ copies overall.

2

A baby is tested for HLA antigens.

Tested HLA Antigens: HLA-A2, 28 ; HLA-B15, 7

Since we are unsure if HLA-A2 came with HLA-B15 or HLA-B7, potential haplotypes are written in ___ ways.

both

Write the possible haplotypes from the tested HLA Antigens: HLA-A2, 28 ; HLA-B15, 7

HLA-A2, B15 and HLA-A28, B7 or HLA-A2, B7 and HLA-A28, B15

Either possible haplotype could be correct, ___ studies must be conducted to determine a child’s haplotype.

This process finds which HLA haplotype comes from each parent - often used in ___ tests.

family; paternity

A child who gets HLA-A9 and HLA-B27 from their mother and gets HLA-A11 and HLA-B13 from their father has the following haplotypes:

HLA-A9, B27 and HLA-A11, B13

The previous method for HLA testing involved ___ tests using antibodies for agglutination. However, it is now very hard to do since there is too much ___ in alleles.

serological; variation

The current methods for HLA testing is ___ testing which uses DNA analysis to identify genes. Due to the ___ expression of HLA alleles, genes will __ for HLA protein (MHC).

molecular; codominant; code

HLA nomenclature is written as HLA-___ ___ * ___.

Ex. HLA-DRB1*1301

locus; chain gene if applicable (MHCII); specific allele

(Where - what chain - which allele?)

HLA markers cause ___ in transplantation and matching of organs. Testing for these markers can be used in ___ testing to exclude fatherhood.

issues; paternity

HLA gene codes for MHC___ on cell surface.

MHCI expressed on all ___ cells.

Presentation happens with ___ peptides (viral and tumor antigen peptides made within cell). Signal for CD8+ ___ T Cell to ___ infected cell.

I; nucleated; endogenous; cytotoxic; kill

MHCI is a ___ dimer with two noncovalently linked polypeptide chains: ___ chain and ___ chain.

glycoprotein; alpha; b2-microglobulin

There are ___ domains within the alpha chain in MHCI’s structure.

a1 and a2 make up the alpha ___ - comes together to form peptide ___ site. Peptides are usually ___-10 A.A. long!

a3 is the ___ portion in cell ___!

3; helix; binding; 8; hydrophobic; membrane

The B₂-microglobulin chain of MHCI is encoded by a single gene in chromosome ___ and sits on the ___ of cell.

Essential for ___ of a-chain! Without it, alpha chain ___ properly make peptide binding cleft.

15; surface; folding

CD8 binds to ___ on MHCI.

a3

In MHCI presentation, ___ viral/tumor protein gets degraded and antigen-processed by ___ into peptides.

Peptides are transported to the ___ ___ where it binds to ___. The Peptide-MHCI complex is then transported to the ___.

From the Golgi, the complex is transported to the cell ___ where Cytotoxic T cell’s ___ binds to antigen and MHC I’s a domain binds to ___.

The CD8 T Cell then lyses the cell via ___ and granzyme.

endogenous; proteasome

Rough ER; MHCI; golgi

surface; TCR; CD8

perforin

Non-classical class I antigens include HLA-E, F, G antigens.

E,F: not expressed on cell surfaces
G: ___ placenta from mother’s immune system by sending ___ signals to NK cells.

protects; inhibitory

The Role of MHCI molecules is to bind viral/tumor peptides in ___ and present peptide to ___ T cell.

___-___ identical antigen-MHC I complexes will induce a cytotoxic ___. After contact, CD8 T cells produce ___ and ___ to lyse cells.

ER; cytotoxic

10; 100; response; granzyme; perforin

MHCII are expressed on ___ ___ cells including B cells, monos and macros, and dendritic cells.

Presentation happens with ___ peptides where antigen is processed from the outside like extracellular bacteria.

Antigen Presenting; exogenous

MHCII structure includes a ___ and ___ chain that are inserted into the cell’s ___. MCHII-Peptide binding occurs in the ___ compartment.

alpha; beta; membrane; endosomal

MHCII a1 and b1 domains form the peptide ___ site, a ___ pocket than MHCI. Here, longer peptides fit ___-18 A.A long.

binding; deeper; 13

CD4 binds to ___ region on MHCII.

B2

Just like MHC I, there are ___ MHCII molecules as well - just not focused on.

nonclassical

In MHCII presentation, ___ protein gets taken up by ___ or phagocytosis and antigen processed into peptides in the ___.

MHCII is located in the ___ ___ but binding is blocked by ___ chain. MHCII leaves rough ER through ___ and fuses with ___. Endosome then ___ invariant chain where Peptide-MHCII complex can ___ together.

Peptide-MHCII complex transported to cell surface where CD4+ ___ T Cell’s TCR binds to antigen and MHCII’s ___ domain binds to CD4.

exogenous; endocytosis; endosome

Rough ER; invariant; golgi; endosome; cleaves; bind

Helper; B2

The role of MHCII molecules is to bind MHCII-TCR to trigger T helper cells ___ and B cell response including proliferation and ___ formation.

proliferation; antibody

The clinical significance of MHC is that it can trigger responses that lead to ___ rejection. It also provides a link between certain ___ antigens and ___ disease. It is important to note that small ___ differences in proteins change ability to react to foreign antigens.

graft; MHC; autoimmune; biochemical