Methods and compositions useful in generating non canonical CD8+ T cell responses

A method of generating CD8+ T cells that recognize MHC-E-peptide complexes, the method comprising:

• (1) administering to a first subject a recombinant cytomegalovirus (CMV) in an amount effective to generate a first set of CD8+ T cells that recognize MHC-E/peptide complexes, wherein the recombinant CMV vector comprises (a) a first nucleic acid sequence encoding at least one heterologous antigen;
• (b) a second nucleic acid sequence encoding at least one active UL40 protein, or an ortholog or homolog thereof;
• and (c) a third nucleic acid sequence encoding at least one active US28 protein, or an ortholog or homolog thereof;
• wherein the CMV vector does not express an active UL128 protein, or an ortholog thereof, and does not express an active UL130 protein, or an ortholog thereof;
• (2) identifying a first CD8+ T cell receptor (TCR) from the first set of CD8+ T cells, wherein the first CD8+ TCR recognizes a MHC-E/heterologous antigen-derived peptide complex;
• (3) isolating a second set of CD8+ T cells from the first subject or from a second subject;
• and
• (4) transfecting the second set of CD8+ T cells with an expression vector, wherein the expression vector comprises a nucleic acid sequence encoding a second CD8+ TCR and a promoter operably linked to the nucleic acid sequence encoding the second CD8+ TCR, wherein the second CD8+ TCR comprises CDR3α and CDR3β of the first CD8+ TCR, thereby generating one or more transfected CD8+ T cells that recognize a MHC-E/heterologous antigen-derived peptide complex.