Molecular un-stability of peptide-MHC complex and activation of T cell

Abstract

CD4+ T cell responses require the recognition of specific peptide-MHC complexes displayed by APC. It is important to determine how Ag presentations affect the ensuing T cell response. Imunization of B10.BR mice with immunodominant peptide 48-61 of Hen egg lysozyme elicit two different types of T cell responses. First type of T cell (type A termed by Unanue et. al) respond to APC pulsed with either peptide or whole HEL protein. Second type of T cell (termed type B) respond to APC incubated with peptide but showed no response to APC with whole protein. Some of the type B T cell clone exhibit unusual response to the variant of 48-61 peptide and responded better to poor MHC binding peptide that to strong MHC binding peptide. In contrast, reactivity of the type A of T cell clones correlate well with the affinity of the peptide to the MHC molecules. Since weak MHC binding peptides form unstable complex, we hypothesize that T cells, like type B T cell, respond well to unstable MHC peptide complex by interacting with one of multiple transitional conformations. To test this hypothesis, we observed the movement of peptide/MHC complex at the single molecular level by using diffracted X-ray tracking (DXT) method. It was found that movement of the low affinity peptide MHC complex was greater than that of high affinity peptide MHC complex. However, the difference between two complexes was mainly due to the overall movement of the molecule rather than the different movement of the peptides in the MHC groove. Thus, peptide bound to the MHC greatly influence the movement of the whole MHC peptide complex and this movement strongly affect the recognition by T cell.