N-terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava-F7(776-788)], aid differentiation of E75-TCR+CD8+ cells to perforin-positive cells.
The objective of this study was to discover whether the peptides LRMK and LRMK-Ava linked to the N-terminus of peptides HER-2 (774-788) and HER-2 (776-788), respectively, help differentiation of E75-TCR(+)CD8(+) cells. Activation was quantified in terms of proliferation of E75-TCR(+)CD8(+) cells expressing high, medium and low density amounts of the specific TCR. Differentiation to functional CD8(+) cells was quantified as induction of Perforin (Perf), the lytic-enzyme which mediates the effector function of CD8(+) cells, in E75-TCR(+)CD8(+) cells. Peripheral blood mononuclear cells (PBMCs) of 3 patients activated with E75(+)AE-37 and E75(+)AE-47 more greatly increased the number of E75-TCR(Hi) CD8(+)Perf(+) cells than PBMCs activated by AE-47 alone or AE-47(+) E75. E75 plus cytokines and cytokines alone activated more E75-TCR(Low) cells than did AE-37 and AE-47. E75(+) AE-37 and AE-37 also induced differentiation of small- and medium-size activated CD8(+) cells from BRC ascites, in allogeneic activation, to Perf(+) cells. Preferential differentiation of E75-TCR(+)CD8(+)Perf(+) cells in distinct patients by AE-37 and AE-47 indicates that cancer vaccines will benefit from such correct individual and disease-associated help. Additional studies using the natural peptides p776 and F7 are needed to understand whether the LRMK-(Ava) tetra-, or pentamer augments or inhibits differentiation of CD8(+) cells, compared with native, natural HER-2 peptides and/or protects CD8(+) cells activated by E75 and by other HLA-I bound peptides from death. Our findings also develop a model for uniform quantification of differentiated CD8(+) effectors.
Matsueda
Satoko
S
Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Gao
Hui
H
Efferson
Clayton L
CL
Tsuda
Naotake
N
Ishiyama
Satoshi
S
Li
Yufeng
Y
Ioannides
Maria G
MG
Fisk
Bryan
B
Peoples
George E
GE
Ioannides
Constantin G
CG
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000494:pharmacology*; D054353:Perforin / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
D010446:Peptide Fragments; D054353:Perforin; D018719:Erb-b2 Receptor Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell