Investigating the distinct requirements of ′peptide-receptive′ H-2KK molecules
MHC class I peptide presentation enables constant surveillance of intracellular alterations, such as virus infection and tumour appearance, by CD8+ T cells. Correct assembly of MHC class I-peptide complexes in the endoplasmic reticulum (ER) requires a sophisticated ′peptide-loading complex′ (PLC). The current model of PLC comprises the proteins: transporter associated with antigen processing (TAP) 1 and 2, tapasin, calreticulin, ERp57, tapasin related protein (TAPBPR) and the MHC I heavy chain (HC)/β2-microglobulin (β2m) heterodimer.
Interestingly, we have observed that H-2Kk-restricted CD8+ T cellsconsistently display 100-fold lower affinity (compared to T cell restricted to other H-2 alleles) for cognate peptide pulsed targets due to limited ′peptide-receptive′ H-2Kk on the cell surface. Our goal is to identify the intracellular components that sequester ′peptide-receptive′ H-2Kk in the ER. Such knowledge may enhance our capacity to design better cancer and viral vaccines.