A TUMOR ESCAPE VARIANT THAT HAS LOST ONE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I RESTRICTION ELEMENT INDUCES SPECIFIC CD8-CELLS TO AN ANTIGEN THAT NO LONGER SERVES AS A TARGET( T)
S. Seung et al., A TUMOR ESCAPE VARIANT THAT HAS LOST ONE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I RESTRICTION ELEMENT INDUCES SPECIFIC CD8-CELLS TO AN ANTIGEN THAT NO LONGER SERVES AS A TARGET( T), The Journal of experimental medicine, 178(3), 1993, pp. 933-940
After loss of expression of a major histocompatibility complex class I
K(k) allele, the escape variant of an immunogenic tumor grows progres
sively in normal mice. This progressor variant is resistant to killing
by cytotoxic T lymphocytes (CTLs) directed against the A and B antige
ns presented by K(k). Although the variant retains the expression of t
he D(k) allele and is sensitive to CTLs directed against the C antigen
presented by D(k), the variant failed to induce CTLs to this antigen
in vivo. Instead, the variant induced CD8+ T cells directed to the A a
ntigen. This was shown at the molecular level by T cell receptor beta
chain sequence analysis of the responding cells. Further evidence for
the presence of A antigen in the variant came from the finding that sp
leen cells of mice injected intraperitoneally with the variant tumor c
ells were primed for an anti-A CD8+ CTL response in vivo. Thus, in con
trast to other variants that lost a target antigen and induced a CTL r
esponse to remaining target antigens, the K(k) loss variant continued
to induce an immune response to a tumor antigen that is no longer pres
ented on the tumor cell surface. Even though the variant escapes in a
single step because an effective CTL response to secondary antigens is
prevented, these secondary antigens remain as potential targets of im
munotherapy on the variant's cell surface.