U. Grohmann et al., Immunogenicity of tumor peptides: importance of peptide length and stability of peptide MHC class II complex, CANCER IMMU, 48(4), 1999, pp. 195-203
Nonameric P815AB, a cytotoxic-T-lymphocyte-defined minimal core peptide enc
oded by the murine mastocytoma gene P1A, fails to initiate CD4(+) cell-depe
ndent reactivity in vivo to class-I-restricted epitopes when mice are admin
istered peptide-pulsed dendritic cells. Effective immunization requires T h
elper effects, such as those mediated by coimmunization with class-II-restr
icted (helper) peptides or by the use of recombinant interleukin-12 (rIL-12
). Although P815AB does possess class-II-restricted epitopes, they are like
ly suboptimal, resulting in poor affinity and/or stability of MHC/P815AB co
mplexes and inadequate activation of the antigen-presenting cell function o
f dendritic cells. The present study has examined a series of:longer, P815A
B-centered peptides (11-14 amino acids in length, all P1A-encoded) for thei
r ability to initiate CD4(+) and CD8(+) cell-mediated responses to the nona
mer in vivo, their ability to bind class II MHC in vitro, and their ability
to assemble class II molecules stably. By means of a class-I-restricted sk
in test assay in mice receiving peptide-pulsed dendritic cells, we found th
at a 12-mer and a 13-mer effectively immunized against the core P815AB pept
ide, and that this correlated with IL-2 production in vitro by CD4+ cells i
n response to the nonamer. In vitro studies, involving affinity-purified cl
ass II molecules, showed that the capacity to assemble class II molecules s
tably, more than the affinity for class II MHC, correlated with the ability
of the different P815AB peptides to prime the host to the core peptide see
n by the T cells.