MHC Flashcards

Questions and Answers

What are the structural differences between MHC class I and MHC class II molecules?

MHC Class I is composed of α₁, α₂, α₃, and β₂, binds to CD8, and α₁ and α₂ form the peptide binding grove. MHC Class II is composed of α₁, α₂, β₁, and β₂, binds to CD4 at β₂, and α₁ and β₁ form the peptide binding grove.

On which MHC molecule are exogenous and endogenous antigens presented?

Endogenous antigens are presented in the context of MHC class I while exogenous antigens are presented in MHC class II.

Which cells express MHC class I molecules?

All nucleated cells and platelets express MHC class I.

Which cells express MHC class II molecules?

Predominantly on antigen-presenting cells (APC) such as dendritic cells, B cells, and macrophages. Signup and view all the answers

How are MHC alleles expressed and inherited?

HLA genes are expressed co-dominantly with one haplotype inherited from each parent. Signup and view all the answers

How do polymorphisms and polygeny contribute to the diversity of MHC molecules expressed by an individual?

Variation between MHC allotypes is concentrated in the sites that bind peptide and the TCR. Signup and view all the answers

Describe the advantage of MHC heterozygosity.

It grossly increases the ability to recognize an array of peptides. Signup and view all the answers

What role do MHC molecules play in transplant rejection?

MHC class I and II isotypes are matched closely to prevent a strong T cell response against foreign molecules. Signup and view all the answers

What is the function of the MHC?

To present antigens to T cells. Signup and view all the answers

What are TAP1 and TAP2?

Genes that encode the transport associated with antigen processing, required for peptide transport into the ER for loading onto MHC class I. Signup and view all the answers

How are cytotoxic CD8 T cell responses generated in response to a viral infection?

Viral antigens are generated intracellularly and presented in the context of MHC class I molecules. Signup and view all the answers

What is cross presentation?

A specialized mechanism by which exogenous antigens are presented in the context of MHC class I molecules. Signup and view all the answers

How are CD8 responses generated if the virus does not directly infect an antigen-presenting cell?

Viral antigens are released from infected cells and taken up by APCs, some are cross-presented to mount a cytotoxic CD8 T cell response. Signup and view all the answers

What prevents peptides in the ER from binding to the MHC class II molecule?

Invariant chain molecule. Signup and view all the answers

What is the function of the invariant chain molecule?

It blocks the binding of peptides to MHC class II molecules until it reaches the site of extracellular breakdown. Signup and view all the answers

Define MHC Class I deficiency.

A recessively inherited immunodeficiency in which MHC class I is expressed at very low levels, leading to a severe deficiency in CD8 T cells. Signup and view all the answers

Define MHC class II deficiency.

Also known as Bare Lymphocyte syndrome, it is an autosomal recessive trait leading to a deficiency in CD4 T cells. Signup and view all the answers

What is HLA?

Human Leukocyte Antigen, a genetic designation for MHC. Signup and view all the answers

What is polymorphism?

The existence of different variants of a gene; two or more different forms or alleles of a gene. Signup and view all the answers

What are alleles?

Natural variants of a gene; one of several alternate forms of a gene at a single locus. Signup and view all the answers

What is a haplotype?

The set of polymorphic genes carried on a single chromosome. Signup and view all the answers

What are the most polymorphic MHC Class I isotypes?

HLA-A, HLA-B, HLA-C. Signup and view all the answers

What are the most polymorphic MHC Class II isotypes?

HLA-DP, HLA-DQ, HLA-DR. Signup and view all the answers

What is the difference between graft versus host disease and transplant rejection?

In transplant rejection, the recipient's T cells attack the transplant. In graft versus host disease, T cells in the transplant attack the recipient's tissues. Signup and view all the answers

Study Notes

Structural Differences Between MHC Class I and Class II

MHC Class I consists of α₁, α₂, α₃, and β₂ subunits.
MHC Class II contains α₁, α₂, β₁, and β₂ subunits.
MHC Class I binds CD8, while MHC Class II binds CD4 at the β₂ subunit.
Peptide binding grooves are formed by α₁ and α₂ in Class I, and α₁ and β₁ in Class II.

Antigen Presentation

Endogenous antigens, from within the cell, are presented via MHC Class I after loading peptides in the ER.
Exogenous antigens enter externally and are presented via MHC Class II after being processed in acidified endocytic vesicles.

Expression of MHC Molecules

All nucleated cells and platelets express MHC Class I.
MHC Class II is predominantly found on antigen-presenting cells (APCs), including dendritic cells, B cells, and macrophages.
Activated T cells and thymic epithelium can also express MHC Class II.

Inheritance and Diversity of MHC Alleles

HLA genes are co-dominantly expressed, one haplotype inherited from each parent.
Variation in MHC allotypes is notably concentrated at peptide and TCR binding sites, enhancing diversity.

Advantages of MHC Heterozygosity

Heterozygosity significantly increases the ability to recognize a broader range of peptides.

MHC in Transplant Rejection

Matching MHC Class I and II is crucial for transplants to minimize rejection, as a strong T cell response occurs against "foreign" MHC molecules.

MHC Function and Transport

The primary function of MHC molecules is to present antigens to T cells.
TAP1 and TAP2 genes are responsible for transporting peptides into the ER for MHC Class I loading.

Cytotoxic T Cell Responses

Cytotoxic CD8 T cell responses are triggered when viral antigens, presented by MHC Class I molecules, are recognized.
Cross-presentation allows extracellular antigens to be presented on MHC Class I, important for vaccine design.

Mechanisms Preventing Inappropriate Binding

The invariant chain prevents premature binding of peptides to MHC Class II until reaching endocytic vesicles.
HLA-DM facilitates the release of the CLIP fragment, allowing peptide binding.

MHC Deficiencies

MHC Class I deficiency leads to severely reduced CD8 T cells, increasing vulnerability to respiratory viral infections.
MHC Class II deficiency, or Bare Lymphocyte syndrome, results in increased susceptibility to pathogens and deficient CD4 T cell counts, often manifesting as severe combined immunodeficiency (SCID).

Polymorphism and Alleles

Polymorphism refers to the presence of multiple gene variants, enhancing genetic diversity.
Alleles are different forms of a gene at a single locus.

Haplotype Overview

A haplotype denotes a set of polymorphic genes on one chromosome, with humans having two inherited haplotypes.

Most Polymorphic MHC Isotypes

MHC Class I: HLA-A, HLA-B, HLA-C.
MHC Class II: HLA-DP, HLA-DQ, HLA-DR.

Graft Versus Host Disease vs. Transplant Rejection

In kidney transplants, recipient T cells attack the transplanted kidney.
In bone marrow transplants, T cells from the transplant attack the recipient's tissues.

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Description

Test your understanding of MHC class I and II molecules with this quiz. Explore the structural differences and learn about antigen presentation by these critical components of the immune system. Perfect for students of immunology and related fields.