Effect of Molecular Sway on the Recognition of Peptide/MHC Complex by T Cells

Abstract

CD4+ T cell responses require the recognition of specific peptide-MHC complexes displayed by APC. It is important to determine how antigen presentations affect the ensuing T cell response. Immunizations of B10.BR mice with naturally processed 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 pulsed with whole protein. Reactivity of the type A T cell clones correlated well with the affinity of the peptide to the MHC molecules. However, some type B T cell clone exhibit better response to the low affinity truncated (52-61) peptide than to high affinity peptide (48-61). Since weak MHC binding peptides form unstable complex, we hypothesize that type B T cells respond to the transitional conformations generated by unstable peptide/MHC complex. To test this hypothesis, we analyzed 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 complexes was different from that of high affinity peptide/MHC complexes. Moreover, comparison of the movement of a series of low affinity peptide/MHC complexes revealed clear correlation between magnitude of twisting movement of peptide and T cell recognition. Thus, our results clearly demonstrated that movement of peptide in MHC strongly affects to T cell recognition and some but not all T cells recognize a transitional conformation generated by weak binding peptides.