(i) Describe the structure of an MHC class I molecule, identifying the different polypeptide chains and domains. (ii) What are the names of the MHC class I molecules produced by humans?
Which part of the molecule is encoded within the MHC region of the genome? (iii) Which domains or parts of domains participate in the following: antigen binding; binding the T-cell receptor; and binding the T-cell co-receptor? (iv) Which domains are the most polymorphic?
What will be an ideal response?
(i) The complete MHC class I molecule is a heterodimer made up of one ? chain and a smaller chain called ?-microglobulin. The ? chain consists of three extracellular domains ?1, ?2, and ?3—a transmembrane region and a cytoplasmic tail. ?2-Microglobulin is a single-domain protein noncovalently associated with the extracellular portion of the ? chain, providing support and stability. (ii) The polymorphic class I molecules in humans are called HLA-A, HLA-B, and HLA-C. The ? chain is encoded in the MHC region by an MHC class I gene. The gene for ?2-microglobulin is elsewhere in the genome. (iii) The antigen-binding site is formed by the ?1 and ?2 domains, the ones farthest from the membrane, which create a peptide-binding groove. The region of the MHC molecule that binds to the T-cell receptor encompasses the ? helices of the ?1 and ?2 domains that make up the outer surfaces of the peptide-binding groove. The ?3 domain binds to the T-cell co-receptor CD8. (iv) The most polymorphic parts of the ? chain are the regions of the ?1 and ?2 domains that bind antigen and the T-cell receptor. ?2-Microglobulin is invariant; that is, it is the same in all individuals.
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