Major Histocompatibility Complex in Immunology

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Questions and Answers

What amino acids are recognized by the hydrophobic pocket at the C-terminal end of MHC class I molecules?

Val, Ile, Leu, or Met (correct)

Ala, Gly, Ser, or Thr

His, Trp, Phe, or Tyr

Asp, Glu, Lys, or Arg

What is a requirement for peptide binding to MHC class II molecules?

Peptides must be shorter than 10 amino acids.

Peptides must be predominantly hydrophobic.

Peptides must contain a basic residue at the C terminus.

Peptides must extend beyond the floor of the cleft. (correct)

What role do MHC molecules play in immune response?

They directly kill infected cells.

They bind peptide antigens for recognition by T cell receptors. (correct)

They produce antibodies to neutralize pathogens.

They transport nutrients to T cells.

Which statement is true about the interaction of peptides with MHC class I molecules?

Class I binding requires specific amino acid residues near the C terminus. Signup and view all the answers

What accounts for the MHC restriction of T cells?

The MHC residues involved in peptide binding. Signup and view all the answers

What is the primary role of MHC molecules in the immune system?

They act as antigen-presenting structures. Signup and view all the answers

Which classes of MHC genes are responsible for presenting antigens to TC cells?

Class I MHC genes Signup and view all the answers

Where are MHC genes located in humans?

Chromosome 6 Signup and view all the answers

What effect do MHC molecules have on organ transplant compatibility?

They play a role in donor-recipient tissue compatibility. Signup and view all the answers

Which class of MHC genes is primarily expressed on macrophages and dendritic cells?

Class II MHC genes Signup and view all the answers

How do MHC molecules influence the immune response to infectious organisms?

They partly determine the response based on presented antigens. Signup and view all the answers

What kind of glycoproteins do Class I MHC genes encode?

Glycoproteins on the surface of nearly all nucleated cells Signup and view all the answers

What is a consequence of an individual's specific set of MHC molecules?

It influences their susceptibility to diseases. Signup and view all the answers

What is the primary function of non-classical class I HLA-G molecules?

To facilitate fetal protection from maternal T cell rejection Signup and view all the answers

Which of the following best describes the expression of classical and non-classical molecules?

Classical molecules are expressed on all cell types, while non-classical molecules are limited to specific types. Signup and view all the answers

What genetic characteristic is true about MHC genes?

MHC genes are characterized by a high level of polymorphism. Signup and view all the answers

What occurs less frequently within the H-2 complex?

Crossover and recombination Signup and view all the answers

What defines a haplotype in the context of MHC genes?

A unique set of alleles at a specific locus inherited from one parent Signup and view all the answers

Which of the following statements about F1 mice and graft acceptance is true?

F1 mice are incapable of accepting grafts from either parental strain. Signup and view all the answers

What distinguishes Class III MHC molecules from Class I and Class II molecules?

Class III molecules are unrelated proteins with no common function. Signup and view all the answers

Which factor contributes to the identification of rare identical sets of HLA genes?

The probability of mismatched haplotypes in unrelated individuals Signup and view all the answers

What is the main source of peptide fragments presented by MHC class I molecules?

Proteins synthesized within the cell Signup and view all the answers

What is true about the interaction between MHC molecules and peptides?

Peptides are bound in an extended conformation Signup and view all the answers

What characteristic of peptide binding to MHC molecules enhances T cell recognition?

Peptides contain specific amino acid residues Signup and view all the answers

How many different MHC class I alleles are typically present in a heterozygous individual?

6 Signup and view all the answers

Which statement accurately describes the peptide-MHC complex activation of T cells?

As few as 100 complexes can initiate a specific T cell response Signup and view all the answers

What type of interactions mediates the binding of peptides to MHC molecules?

Noncovalent interactions Signup and view all the answers

What aspect of MHC class I molecules allows for greater variability in recognized peptides?

The bulging of longer peptides accommodates different residues Signup and view all the answers

Which of the following best describes the peptide-binding cleft characteristics of MHC molecules?

The cleft can bind only one peptide at a time Signup and view all the answers

How is the peptide-MHC association described?

Saturable with a slow off-rate Signup and view all the answers

What percentage of total class II molecules on the surface of an APC typically represent a specific peptide?

0.1% Signup and view all the answers

Study Notes

Major Histocompatibility Complex (MHC)

MHC codes for cell surface proteins essential for the adaptive immune system in mammals.
Mammalian MHC products play roles in intercellular recognition, differentiating self from non-self.
MHC participates in both humoral and cell-mediated immune responses.
T-cells recognize antigens only when combined with an MHC molecule.
MHC molecules act as antigen-presenting structures.

MHC Interactions

MHC molecules mediate interactions between leukocytes and other leukocytes or body cells.
MHC determines donor compatibility for organ transplants.
MHC is linked to susceptibility to diseases and the development of autoimmunity.
A particular set of MHC molecules influences the repertoire of antigens that a person's T cells can respond to.
MHC partly determines an individual's response to infectious organisms.

MHC Genes

In humans, MHC genes are located on chromosome 6, referred to as HLA.
In mice, MHC genes are located on chromosome 17, referred to as the H-2 complex.
MHC genes in humans and mice are arranged differently but grouped into regions encoding three classes of molecules.
- Class I MHC genes encode glycoproteins expressed on nearly all cell surfaces.
- Class II MHC genes encode glycoproteins expressed on macrophages and dendritic cells.
- Class III MHC genes encode secreted proteins involved in the complement system and inflammation.

Class I and Class II MHC Molecules

Class I and Class II MHC molecules are membrane-bound glycoproteins that are unrelated but don't share structural similarities or common functions.
Class I MHC molecules display a wider range of cell types than Class II MHC molecules.
Non-classical MHC Class I molecules are expressed in limited specific cell types compared to classical MHC Class I molecules.

Characteristics of Peptide-MHC Interactions

MHC molecules show a broad specificity to peptide binding.
A single MHC allele can present many different peptides to T cells.
A single T cell recognizes only one possible MHC-peptide complex.
Each MHC class I or II molecule has a single peptide-binding cleft to bind to a single peptide.
MHC molecules present peptides derived from proteins made by the cell or internalized via phagocytosis or pinocytosis.
Peptides that bind to MHC molecules share structural features.
Peptide size and amino acid residues influence peptide binding to a specific MHC molecule.

Association of Peptides with MHC Molecules

Peptide association with MHC molecules is saturable and slow.
The number of peptide-MHC complexes activating specific T lymphocytes are small.
Only a small fraction of complexes will contain the same peptide.
A few complexes (around 100) containing the same peptide can initiate a specific response.
MHC molecules display self and non-self.

Structural Basis of Peptide Binding to MHC Molecules

Peptide binding to MHC molecules is mediated by non-covalent interactions, electrostatic interactions, hydrogen bonding, and van der Waals interactions.
Peptides bind to MHC clefts in extended conformations.
Bound peptides and associated water molecules fill the clefts, interacting extensively with amino acid residues in the MHC cleft.

MHC Molecules in Cells

MHC molecules assemble within the cell.
MHC class I molecules associate with short peptide fragments.
MHC class II molecules associate with proteins internalized by the cell via phagocytosis or pinocytosis.

Allelic Forms of MHC

MHC genes are polymorphic.
Human MHC loci are closely linked.
Crossover occurs only once per 200 mitotic events.
Each set of alleles is called a haplotype.
Haplotypes are inherited from both parents.
A new haplotype can arise from recombination of parental haplotypes.
Inbred strains have identical sets of MHC genes.

Presentation of MHC molecules

Longer peptides bulge in the middle, while shorter ones are more extended.
Contacts with MHC molecules are via hydrogen bonds to anchor residues.
Class I MHC molecules have peptide residues recognized by specific T cells with hydrophobic pockets.
Class II MHC molecules interact with peptides, forming hydrogen bonds or charge interactions. MHC molecules extend beyond the cleft floor, binding longer peptides.

MHC Response and Peptide Binding

MHC genes are immune response genes.
Only individuals with MHC molecules that can bind a specific peptide can present this peptide.
Peptides define antigen specificity.
MHC residues are involved in MHC restriction and T cell recognition.
Peptide-binding domains of MHC I & II differ. Class I requires specific amino acids near N and C termini. No such requirement for class II peptide binding.

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Description

This quiz explores the Major Histocompatibility Complex (MHC) and its critical role in the adaptive immune system of mammals. You'll learn about MHC's functions in antigen presentation, organ transplant compatibility, and its implications for autoimmune diseases and infectious responses.