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Questions and Answers
What is the probability that two siblings will share no haplotype?
What is the probability that two siblings will share no haplotype?
Which part of the MHC Class I molecule binds CD8 cells?
Which part of the MHC Class I molecule binds CD8 cells?
What type of antigens can induce a weak immune response due to their amino acid variations?
What type of antigens can induce a weak immune response due to their amino acid variations?
What is the function of the peptide-binding groove formed by the α1 and α2 domains in MHC Class I molecules?
What is the function of the peptide-binding groove formed by the α1 and α2 domains in MHC Class I molecules?
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What distinguishes the α chain and β chain domains in MHC Class II molecules?
What distinguishes the α chain and β chain domains in MHC Class II molecules?
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Which of the following statements is true about HLA genes?
Which of the following statements is true about HLA genes?
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How many amino acids can the peptide-binding groove of MHC Class II molecules typically bind?
How many amino acids can the peptide-binding groove of MHC Class II molecules typically bind?
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What allows for the co-dominant expression of HLA genes?
What allows for the co-dominant expression of HLA genes?
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What is the primary role of Major Histocompatibility Complex (MHC) in the immune system?
What is the primary role of Major Histocompatibility Complex (MHC) in the immune system?
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Which of the following correctly identifies the classes and loci of MHC genes?
Which of the following correctly identifies the classes and loci of MHC genes?
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How does the inheritance of HLA antigens occur among individuals?
How does the inheritance of HLA antigens occur among individuals?
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What is the primary function of MHC class II molecules?
What is the primary function of MHC class II molecules?
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What differentiates Class I MHC antigens from Class II MHC antigens in terms of their distribution?
What differentiates Class I MHC antigens from Class II MHC antigens in terms of their distribution?
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Which factor is NOT relevant to the acceptance or rejection of tissue and organ transplants?
Which factor is NOT relevant to the acceptance or rejection of tissue and organ transplants?
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How are MHC genes expressed in individuals?
How are MHC genes expressed in individuals?
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Which of the following correctly describes the properties of HLA proteins?
Which of the following correctly describes the properties of HLA proteins?
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Which type of T-cell is primarily activated by MHC class I molecules?
Which type of T-cell is primarily activated by MHC class I molecules?
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What significant discovery related to the Major Histocompatibility Complex earned Snell a Nobel Prize in 1980?
What significant discovery related to the Major Histocompatibility Complex earned Snell a Nobel Prize in 1980?
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What is the significance of MHC restriction in immunological responses?
What is the significance of MHC restriction in immunological responses?
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What is meant by the term 'alloantigens' in the context of HLA proteins?
What is meant by the term 'alloantigens' in the context of HLA proteins?
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What does polymorphic mean in the context of MHC genes?
What does polymorphic mean in the context of MHC genes?
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Which HLA class I molecule has the highest number of variant alleles according to the IMGT-HLA database?
Which HLA class I molecule has the highest number of variant alleles according to the IMGT-HLA database?
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Why might certain HLA alleles be more common in individuals with specific diseases?
Why might certain HLA alleles be more common in individuals with specific diseases?
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What is a characteristic feature of the MHC class II antigen presentation pathway?
What is a characteristic feature of the MHC class II antigen presentation pathway?
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Which disease is associated with the HLA-DR3 allele?
Which disease is associated with the HLA-DR3 allele?
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What is the primary use of HLA typing in transplantation?
What is the primary use of HLA typing in transplantation?
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What is a characteristic of serology methods in HLA typing?
What is a characteristic of serology methods in HLA typing?
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Which allele is associated with a significantly higher relative risk for ankylosing spondylitis?
Which allele is associated with a significantly higher relative risk for ankylosing spondylitis?
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Which technique is considered more precise for HLA typing?
Which technique is considered more precise for HLA typing?
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Study Notes
Major Histocompatibility Complex (MHC)
- MHC, also known as Human Leukocyte Antigen (HLA), is a group of genes responsible for coordinating immune response and recognizing "self" from "non-self" antigens.
- MHC genes are located on the short arm of chromosome 6.
- MHC proteins are membrane-bound glycoproteins.
- Success of tissue and organ transplants depends on the similarities between donor and recipient's HLA genes.
- Individuals who are identical at their MHC locus will accept grafts from one another, and individuals who differ at their MHC loci will reject such grafts.
Classes of MHC genes
- Class I MHC: includes 3 main loci (A, B, and C)
- Class II MHC: includes 3 main loci (DP, DQ, and DR)
- Class III genes contain immunologically important genes, encoding two cytokines (tumor necrosis factor and lymphotoxin) and two complement components (C2 and C4).
HLA expression on cells
- Class I HLA: Expressed on all nucleated cells, including leukocytes, but not sperm or red blood cells.
- Class II HLA: Expressed on antigen-presenting cells (APCs) like monocytes, macrophages, dendritic cells, B lymphocytes, some endothelial cells and activated T cells.
Inheritance of HLA-antigens
- HLA inheritance follows Mendelian rules.
- Each person inherits two haplotypes (sets of HLA genes) from their parents— one paternal and one maternal.
- HLA genes are very diverse (polymorphic).
- Each individual inherits only one allele at each locus from each parent.
co-dominant expression of HLA genes:
- Both alleles from each parent are expressed equally.
Minor antigens
- Minor antigens are normal body proteins with slight amino acid differences between individuals.
- They induce a weak immune response but can cause slow graft rejection.
- There are no laboratory tests for minor antigens.
Molecular structure of MHC antigens
MHC Class I molecule structure
- Composed of a 45-kDa α chain and a 12-kDa β2-microglobulin molecule.
- The α chain has three external domains: α1, α2, and α3, a transmembrane segment, and a short intracellular tail.
- α1 and α2 domains form the peptide-binding groove.
- The antigen-binding groove binds to 8-10 amino acid peptides derived from endogenous antigens.
- α3 is the constant region that binds CD8 cells.
MHC class II structure
- Contains two different polypeptide chains: a 33-kDa α chain and a 28-kDa β chain.
- Both chains have a transmembrane segment and two external domains: α1 and α2 (α chain) and β1 and β2 (β chain).
- Each chain has a transmembrane portion and a tail (cytoplasmic part).
- α1 and β1 domains form the peptide-binding groove which binds to 13-18 amino acids derived from exogenous antigens.
- β2 is the constant region that binds CD4 cells.
- MHC antigens are sometimes called Histoglobulins due to their structural similarity to immunoglobulins.
Functions of MHC
- Both class I and class II MHC molecules bind peptides derived from self or non-self antigens and transport them to the cell surface for presentation to T cells via T cell receptors (TCR).
- MHC molecules ensure that T cells only recognize cell-associated protein antigens and that the correct type of T cell (helper or cytotoxic) responds.
T cells role in accordance with MHC complex:
- MHC I presents endogenous peptide antigens to CD8+ T cells (cytotoxic T cells that can kill cells presenting pathogen-derived peptides).
- MHC II primarily presents exogenous antigenic peptides to CD4+ T cells (helper T cells that stimulate B cells to produce antigen-specific antibodies).
Properties of MHC Genes and Proteins:
- MHC genes are highly polymorphic, meaning many different alleles (variants) exist among individuals in a population.
- MHC genes are co-dominantly expressed, meaning the alleles inherited from both parents are equally expressed.
MHC alleles and susceptibility to certain diseases:
- Some HLA alleles occur at higher frequencies in people with certain diseases.
- Diseases associated with particular MHC alleles include autoimmune diseases, susceptibility or resistance to viral diseases, disorders of the complement system, and allergies.
Examples of disease associated with HLA genes:
- Systemic lupus erythematosus (SLE): HLA-DR3.
- Rheumatoid arthritis: HLA-DR4.
- Myasthenia gravis: HLA-B8。
- Type I insulin-dependent diabetes mellitus: DR3/DR4.
- Ankylosing spondylitis: HLA-B27 allele has a 90 times higher relative risk of developing the disease than the general population.
- Celiac disease (gluten allergy): HLA-DQ2 allele has a 50 times higher relative risk of developing celiac disease than the general population.
Indications of HLA typing :
- Transplantation: used to determine HLA compatibility between donor & recipient.
- Disease association: identify the genetic predisposition to certain conditions.
- Paternity testing.
- Anthropological studies (races & nations).
Methods used for HLA-Typing
Serology:
- Antibody-antigen reaction based method using monoclonal antibodies against MHC antigens.
- Quick and cheap but not very specific.
- Examples: microlymphocytoxicity test and mixed leukocyte reaction (MLR).
Molecular (DNA-based typing technique):
- PCR-based techniques that amplify specific DNA fragments.
- More precise & specific, requires well-trained personnel and sophisticated molecular techniques/machines.
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Description
This quiz covers the Major Histocompatibility Complex (MHC), its role in the immune response, and the importance of HLA in tissue and organ transplantation. You will learn about the different classes of MHC genes and their expression on cells. Test your knowledge on the coordination of immune response and the specifics of MHC loci.
