Expression and recognition of HLA-DR/Her-2 complexes on carcinoma cells

Abstract

Cancer patients frequently generate cellular immune response to Her-2, a protein implicated in promoting tumor growth. While 40% of cancers express HLA class II, the ability of class II⁺ tumor cells to process endogenous Her-2 and present immunogenic peptides for CD4⁺ T cell recognition is unknown. We addressed this question using a CD4⁺ T cell clone (TCL-6Dn) restricted to Her-2 peptide 883-899 (p883) presented by HLA-DRβ*0401. We measured the proliferation and cytokine response of TCL-6Dn to p883-loaded and Her-2⁺ tumor cells. Our results showed that TCL-6Dn proliferated strongly to p883-loaded DCs, yet TCL-6Dn lysed tumor cells in a p883-specific manner. Cytokine production analysis showed that TCL-6Dn recognized p883 and produced IFN-γ, GM-CSF, TNF-α and IL-4. Tumor cell lysis was mediated by a soluble factor produced by TCL-6Dn, but cell contact increased lysis. Furthermore, we provide evidence that p883 is a naturally processed HLA class II epitope presented by cancer cells.