DNA sequence analysis of T-cell receptor genes reveals an oligoclonal T-cell response to a tumor with multiple target antigens.

Abstract

Human and murine cancers can express multiple independent antigens as targets for cytolytic T-cells (CTLs). The immune response against one such tumor was studied at the cellular and molecular level by analyzing the T-cell receptor beta chains of CTLs responding in vivo to a murine UV light-induced cancer. A 5-13-fold enhancement of V beta 13+ CTLs above background (naive spleen, 4-5% V beta 13+ among CD8+ T-cells) was demonstrated in the responses of ten individual animals to this tumor. The dominance of V beta 13 usage was exclusively limited to the CD8+ compartment and correlated with recognition of the A but not the B and C antigens on the tumor. In addition, the amino acid sequences of the putative third complementarity determining regions of the T-cell receptor beta chains of CTLs isolated in vivo were remarkably similar to each other suggesting restriction also at the clonal level. Cells responding to four other syngeneic UV-induced tumors, each expressing different unique antigens, or to a variant of the same tumor that had selectively lost the A but retained the independent B and C antigens, induced a 2-fold or less enhancement of V beta 13+ CD8+ cells above background. Thus, the host responds to only one of the several possible target antigens and with relatively few CTL clonotypes.