Major histocompatibility complex (MHC) proteins, antibodies, and T cell receptors are all highly variable so that they can interact with a large number of different antigens. How is variability generated for each of these important antigen-binding proteins?
Answer: MHC proteins are polygenic. Three different loci for the MHCI alpha chain are expressed simultaneously, resulting in the concomitant expression of up to 6 different MHCI on the surface of nucleated cells. MHC II proteins are also polygenic and have 6 different loci. Antibodies and T cell receptors are not polygenic. Each cell expresses only one type of antibody or T cell receptor. Diversity in antibodies and T cell receptors is generated during the maturation process of the B cells (for antibodies) and T cells (for T cell receptors). This diversity is generated by somatic recombination of tandem genes, random reassortment, hypermutation, and imprecise joining of exons during the maturation of T and B cells. Each mature B cell and T cell will express one unique antibody or T cell receptor that was created and selected for during maturation.
Bloom's Taxonomy: 5-6: Evaluating/Creating
Chapter Section: 27.4
1} Design five amino acid peptides that could be bound by a single hypothetical class I MHC protein. The MHC proteins binds peptides that are 10 amino acids long and have two anchor residues, tyrosine and isoleucine, at positions 2 and 5.
Answer: Answers will vary because different amino acids can be used in the motif sequence. However, all five peptides should fit this pattern:
X-Y-X-X-I-X-X-X-X-X
Bloom's Taxonomy: 3-4: Applying/Analyzing
Chapter Section: 27.6
1} Why is the secondary immune response stronger in regard to antibodies?
Answer: Somatic hypermutation creates B cells bearing mutated receptors after the initial exposure to an antigen. These mutated B cells then compete for available antigen. This process selects B cells with receptors having higher antigen-binding strength than the original B cell receptor. This is known as the affinity maturation process and selects for B cells that produce very high affinity antibodies for a specific antigen during secondary exposure.
Bloom's Taxonomy: 5-6: Evaluating/Creating
Chapter Section: 27.4
1} Given that T cell receptors (TCRs) are randomly generated during the maturation process, how are new T cells selected that can recognize self-antigens and other immune cells appropriately?
Answer: Positive selection selects for T cells that can recognize and respond appropriately to MHC-peptide complexes. Positive selection requires the interaction of new T cells in the thymus with the thymic self-antigens. Using their TCRs, some T cells bind to MHC-peptide complexes on the thymic tissue. The T cells that do not bind MHC-peptide complexes undergo apoptosis and are permanently eliminated. By contrast, those T cells that bind thymic MHC proteins receive survival signals and continue to divide and grow. Positive selection retains T cells that recognize MHC-peptide and deletes T cells that do not recognize MHC-peptide and would therefore be unable to recognize MHC-peptide outside the thymus. In the second stage of T cell maturation, T cells must be able to separate from the MHC-peptide complexes in order to continue to divide and grow. If they bind too strongly at this stage, they will not grow or finish maturation and will die. This prevents T cells that may cause immune reactions to self-antigens from maturing and entering the circulation.
Bloom's Taxonomy: 3-4: Applying/Analyzing
Chapter Section: 27.1
Brock Biology of Microorganisms, 15e (Madigan et al.)
Chapter 28 Clinical Microbiology and Immunology
28.1 Multiple Choice Questions
1} Laboratories that work with extremely low risk pathogens are classified as
A) BSL-1.
B) BSL-2.
C) BSL-3.
D) BSL-4.
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