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Optimal Induction of Effector but not Memory Antitumor Cytotoxic T Lymphocytes Involves Direct Antigen Presentation by the Tumor Cells¹

Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210 [X-f. B., X. L., P. Z., Y. L.], and Intituts de Biologie, INSERM U463, 44063, Nantes Cedex 1, France [Y. G.]

MHC class I-restricted tumor antigen can be presented to CD8⁺ T cells by two distinct mechanisms. Direct presentation involves degradation of cytosolic proteins by the proteosome into peptides, transport of the peptides across the endoplasmic reticulum membrane, and expression of the MHC-peptide complex on the tumor cell surface. Cross-presentation, on the other hand, involves uptake and intracellular processing of the tumor antigen by host antigen-presenting cells. Whereas it is clear that cross-presentation is necessary and sufficient for the induction of memory CTLs, it has not been tested whether such presentation is sufficient to induce effector CTLs. Here we analyzed the requirements of direct antigen presentation for the induction of effector and memory antitumor CTLs using a MHC class I^- mutant incapable of direct antigen presentation and its parent, the MHC class I⁺ J558 cell line. We report that in comparison with the MHC class I⁺ tumor cell, the MHC class I^- mutant induces equal priming for recall CTL response but poor effector CTLs. Our results demonstrate that optimal induction of effector CTLs, but not memory CTLs, requires direct antigen presentation by the tumor cells.

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