(i) What would be the outcome if a mutant MHC class I ? chain could not associate with ?2-microglobulin, and (ii) what would happen if the TAP transporter were lacking as a result of mutation? Explain your answers

Question

What will be an ideal response?

Answer 1

(i) If an MHC class I ? chain is unable to bind ?2-microglobulin, it will be retained in the ER and will not be transported to the cell surface. It will remain bound to calnexin and will not fold into the conformation needed to bind to peptide. Thus, antigens will not be presented using that particular MHC class I molecule. (ii) If TAP-1 or TAP-2 proteins are mutated and not expressed, peptides will not be transported into the lumen of the ER. Without peptide, an MHC class I molecule cannot complete its assembly and will not leave the ER. A rare immunodeficiency disease called bare lymphocyte syndrome (MHC class I immunodeficiency) is characterized by a defective TAP protein, causing less than 1% of MHC class I molecules to be expressed on the cell surface in comparison with normal. Thus, T-cell responses to all pathogen antigens that would normally be recognized on MHC class I molecules will be impaired