> Research
> Takayuki Kanaseki[ANTIGEN PROCESSING]
Assistant Professor
Takayuki Kanaseki, M.D. Ph.D.
PROFESSIONAL EDUCATION
Sapporo Medical University, Sapporo, Japan, M.D., 1997
Sapporo Medical University, Sapporo, Japan, Ph.D., 2002
POSTDOCTORAL EXPERIENCE
Division of Immunology, University of California, Berkeley (Dr. Nilabh Shastri Laboratory), 2002-2009
SELECTED PUBLICATIONS
ERAAP and Tapasin independently edit the Amino and Carboxyl termini of MHC Class I peptides.
Kanaseki T, Lind KC, Escobar H, Nagarajan N, Reyes-Vargas E, Rudd B, Rockwood AL, Van Kaer L, Sato N, Delgado JC, Shastri N.
J Immunol. 2013 Jul 17.
(PubMed)
Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells. Blanchard N, Kanaseki T, Escobar H, Delebecque F, Nagarajan NA, Reyes-Vargas E, Crockett DK, Raulet DH, Delgado JC, Shastri N. J Immunol. 2010 Mar 15;184(6):3033-42.
(PubMed)
Endoplasmic reticulum aminopeptidase associated with antigen processing regulates quality of processed peptides presented by MHC class I molecules. Kanaseki T, Shastri N. J Immunol. 2008 Nov 1;181(9):6275-82.
(PubMed)
The final touches make perfect the peptide-MHC class I repertoire. Hammer GE, Kanaseki T, Shastri N. Immunity. 2007 Apr;26(4):397-406.
(PubMed)
ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum. Kanaseki T, Blanchard N, Hammer GE, Gonzalez F, Shastri N. Immunity. 2006 Nov;25(5):795-806.(PubMed)
Circulating CD8+T cells specifically recognize virally infected or tumor cells expressing non-self antigens, therefore the immune surveillance targets and eliminates pathogenic cells without harming healthy host cells. The necessary hallmark of specific recognition is the generation and presentation of peptide / MHC class I complex (pMHCI) on the surface of target cells. Conventional MHC class I peptides are 8-11 mer in length and include MHC class I binding anchor residues, and are precisely generated by the antigen processing mechanisms including proteasomes and ER-resident machineries (figure 1).
Recent researches unveil that the loss of aminopeptidase ERAAP or molecular chaperone Tapasin results in the qualitative change of pMHCI repertoire on the surface, in which a novel set of immunogenic peptides are presented and elicit CD8+T cell responses in wild-type animals, besides many of known pMHCIs expressions are quantitatively reduced. Hence, the MHCI peptide repertoire presented on the surface are readily altered and consequent CD8+ T cell responses are both positively and negatively regulated according to ‘conditions of the antigen processing' in those paticular target cells. These findings are of great interest because the compromised expressions of antigen processing machineries are often observed in pathological conditions such as tumors and autoimmune diseases. Thus, researchers in my group are focusing on 1) the molecular mechanisms of pMHCI generation in pathological conditions, 2) pMHCI processing and disease developments, and 3) applications to clinical treatment: immunotherapy against tumors.
