Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-MHC structural features recognized by cross-reactive T cells
Department of Pathology; Department of Biochemistry and Molecular Pharmacology
Animals; CD8-Positive T-Lymphocytes; Cell Line; Cross Reactions; Crystallography, X-Ray; Epitopes, T-Lymphocyte; Glycoproteins; *Immunity, Heterologous; Immunologic Memory; Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell; Vaccinia; Vaccinia virus
Immunity | Immunology of Infectious Disease | Immunopathology | Pathology
Closely related peptide epitopes can be recognized by the same T cells and contribute to the immune response against pathogens encoding those epitopes, but sometimes cross-reactive epitopes share little homology. The degree of structural homology required for such disparate ligands to be recognized by cross-reactive TCRs remains unclear. In this study, we examined the mechanistic basis for cross-reactive T cell responses between epitopes from unrelated and pathogenic viruses, lymphocytic choriomeningitis virus (LCMV) and vaccinia virus. Our results show that the LCMV cross-reactive T cell response toward vaccinia virus is dominated by a shared asparagine residue, together with other shared structural elements conserved in the crystal structures of K(b)-VV-A11R and K(b)-LCMV-gp34. Based on analysis of the crystal structures and the specificity determinants for the cross-reactive T cell response, we were able to manipulate the degree of cross-reactivity of the T cell response, and to predict and generate a LCMV cross-reactive response toward a variant of a null OVA-derived peptide. These results indicate that protective heterologous immune responses can occur for disparate epitopes from unrelated viruses.
DOI of Published Version
J Immunol. 2013 Nov 15;191(10):5139-52. doi: 10.4049/jimmunol.1300852. Epub 2013 Oct 14. Link to article on publisher's site
Journal of immunology (Baltimore, Md. : 1950)
Shen, Zu T.; Nguyen, Tina T.; Daniels, Keith A.; Welsh, Raymond M.; and Stern, Lawrence J., "Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-MHC structural features recognized by cross-reactive T cells" (2013). Pathology Publications and Presentations. 16.