MHC guide + monoclonal antibody

What does MHC stand for?

Major Histocompatibility Complex.

What is the human MHC called?

HLA = Human Leukocyte Antigen complex.

What chromosome contains the MHC/HLA genes?

Chromosome 6.

What are the three MHC classes?

Class I, Class II, and Class III.

What is the major function of MHC I?

Presents intracellular peptides to CD8+ T cells.

What is the major function of MHC II?

Presents mainly extracellular peptides to CD4+ T cells.

What does MHC III do?

Encodes other immune proteins, including certain complement components and inflammatory mediators. It does not directly encode the classical antigen-presenting molecules.

What chains make up MHC class I?

One α chain + β2-microglobulin.

What chains make up MHC class II?

One α chain + one β chain.

What forms the peptide-binding domain of MHC I?

α1 + α2.

What peptide-binding domain is listed for MHC II in the guide?

α1 + β1.

Is the MHC I peptide-binding groove open or closed?

Closed.

Is the MHC II peptide-binding groove open or closed?

Open at both ends.

What is the typical peptide length for MHC I?

8-10 amino acids.

What is the typical peptide length for MHC II?

13-18 amino acids, often longer.

Where are the anchor residues for MHC I peptides?

At both ends of the peptide.

What shape can an MHC I-bound peptide take?

The middle arches/bulges outward because both ends interact with the MHC.

How is an MHC II-bound peptide positioned?

It is held at a relatively constant elevation above the MHC floor.

What are the classical MHC I genes?

HLA-A, HLA-B, HLA-C.

What are the nonclassical MHC I genes listed in the guide?

HLA-E, HLA-F, HLA-G.

What are the classical MHC II genes?

HLA-DP, HLA-DQ, HLA-DR.

What are the nonclassical MHC II genes listed in the guide?

HLA-DM and HLA-DO.

What characterizes classical MHC molecules?

They are highly polymorphic and perform the major conventional antigen-presentation functions.

What characterizes nonclassical MHC molecules?

They generally perform more specialized functions and are less polymorphic than classical MHC molecules.

What does MHC polymorphism mean?

An MHC gene exists in many different allelic forms within the population.

Approximately how many different MHC variants have been identified in the human population according to the guide?

Several hundred different allelic variants of MHC I and II.

How can a limited variety of MHC molecules present an enormous variety of peptides?

A given MHC molecule can bind numerous different peptides, and some peptides can bind several different MHC molecules.

What is this broad peptide-binding specificity called?

Promiscuous binding.

Why is MHC polymorphism important?

Different MHC variants can bind different sets of peptides, helping populations recognize a wider range of pathogens and affecting tissue compatibility during transplantation.

What is an MHC haplotype?

A group of linked alleles inherited together from one parent.

How many parental HLA haplotypes do you inherit?

One from each parent.

What does heterozygous mean?

The two inherited copies have different alleles at a particular gene.

What does homozygous mean?

Both copies of a particular gene have the same allele.

Can you be heterozygous at one HLA gene but homozygous at another?

Yes.

What does codominant MHC expression mean?

MHC alleles inherited from both parents are expressed.

What is one consequence of codominant HLA expression?

It increases the variety of peptides that can be presented.

What is the endogenous pathway associated with?

MHC I → CD8.

Where do endogenous antigens originate?

Inside the cell.

Where are intracellular proteins broken down in the MHC I pathway?

In the cytoplasm by proteasomes.

Where does peptide loading occur in the MHC I pathway?

Endoplasmic reticulum (ER).

What proteins move peptides into the ER during the MHC I pathway?

TAP1 and TAP2.

What proteins help load peptides onto MHC I?

Chaperone proteins.

What happens after peptide loading onto MHC I?

MHC I reaches the cell surface.

What is the main outcome listed for the MHC I endogenous pathway?

Killing infected cells.

What is the exogenous pathway associated with?

MHC II → CD4.

Where do exogenous antigens originate?

Outside the cell.

Where are extracellular proteins broken down?

Endosomes and lysosomes.

Where does peptide loading occur for MHC II?

Endosome.

What removes CLIP so the antigen peptide can bind MHC II?

HLA-DM.

What is CLIP?

A fragment of the invariant chain that remains in the MHC II groove after the rest of the invariant chain is removed.

What is the function of HLA-DM?

Helps remove CLIP and facilitate antigen-peptide loading onto MHC II.

What is the function of the invariant chain?

Helps guide MHC II to the appropriate compartment and prevents premature binding.

What happens after peptide loading onto MHC II?

MHC II reaches the cell surface.

What is the main outcome listed for the MHC II pathway?

Coordinates the immune response.

What is cross-presentation?

A dendritic cell takes up an extracellular antigen but presents it on MHC I instead of MHC II.

What cell is specifically associated with cross-presentation in the guide?

Dendritic cell.

Which professional APC does the guide identify as especially effective/important for activating T cells?

Dendritic cells.

What important molecules do dendritic cells express?

MHC II and costimulatory molecules.

Which professional APCs are listed in the guide?

Dendritic cells, Macrophages, B lymphocytes.

What can happen to macrophage MHC II and costimulatory molecule expression when macrophages are activated?

Expression can increase.

Do B lymphocytes express MHC II?

Yes.

What general cell population expresses MHC I?

Nearly all nucleated cells.

Is MHC II normally expressed constitutively by all nucleated cells?

No. Only selected cell types normally express MHC II constitutively.

Can B cells recognize antigen directly?

Yes.

What structure does a B cell use to recognize antigen?

Membrane-bound immunoglobulin.

Can B cells bind soluble antigen?

Yes.

What do T cells recognize?

Peptides presented by MHC molecules.

Can T cells bind soluble antigen according to the guide?

No.

What is a monoclonal antibody (mAb)?

A lab-made protein designed to recognize and bind a specific target in the body.

What is the main target of Keytruda in the guide?

PD-1.

What is Keytruda primarily used for in the guide?

Cancer.

What is the listed target of Dupixent?

IL-4α.

What type of disease process is Dupixent associated with in the guide?

Allergic/type 2 inflammatory diseases.

What is the target of Skyrizi?

IL-23.

What disease is Skyrizi associated with in the guide?

Psoriasis.

What is the target of Darzalex?

CD38.

What disease is Darzalex associated with?

Multiple myeloma.

What is the target of Opdivo?

PD-1