Bin Gao
PhD, Professor


Institute of Microbiology
Chinese Academy of Sciences
Datun Road, Chaoyang District, Beijing 100101
Tel / Fax: 86-10-64807599
E-mail: gaob@im.ac.cn

Education
MSc, The Chinese Academy of Military Medicine, China, 1987
PhD, The University of London, 1990-1993
Post-doc, Oxford University, 1993-1996

Career
Research Leader, Peptide Therapeutics plc, Cambridge, 1996-1997
Research Fellow, Institute of Molecular Medicine, Oxford, 1997-2001
Lecturer, University College London, 2001-2005
Currently, Director of the Center for Molecular Immunology, IMCAS

Research Interests
The immune system works by recognising the presence of an invading
organism. To distinguish between normal cells and invaded cells,
immune cells, including Cytotoxic T Lymphocyte (CTL) and Natural
Killer (NK) cell, keep checking an identity marker called Major
Histocompatibility Complex (MHC) class I molecule on the surface of
all nucleated cells. If cells are invaded by viruses, bacteria, or
parasites, a piece of material from the invader will be loaded onto
the MHC complex, the T cell will recognize this change and kill the
host cells with pathogens. By contrast, if cells fail to express
normal MHC on the surface, for example down-regulation by some
viruses, or transformed cells, NK cells will be activated to attack
them. However, in certain situations, CTL and NK are provoked against
normal cells leading to autoimmune disease. MHC class I Antigen
processing Provision of peptide loaded MHC class I molecules to
CD8 T-cells and NK cells play an important role in shaping our
immune system against infection and tumour but not ourself.
Assembly of a particular peptide with MHC class I molecules is
highly coordinated process involving several critical steps
including: the supply of peptides, the generation of peptide
receptive class I molecules, the loading of peptide onto class I
molecules and ER exit of loaded class I to the surface of cell.
Peptides are generally derived from newly synthesized polypeptides
located in the cytosol where they are cleaved by the proteasome and
other proteases. The position of cleavage generally produces
peptides which are extended at the N-terminus but have the correct
C-terminus. Perhaps assisted by cytoplasmic chaperones, these
peptides are transported by TAP into the ER and the extra N-terminal
residues are removed by an aminopeptidase in the ER (ERAAP). MHC
class I heavy chain synthesised in the ER is initially bound by the
chaperone calnexin and subsequently forms a heterodimer with
beta-2-microglobulin (B2m) and is found in association with
calreticulin, tapasin, ERp57 and the Transporter associated with
Antigen Processing (TAP). However, how peptides in the ER amount to
peptide-receptive class I molecules and trigger the loaded class I
complex release from peptide loading complex to appear on the surface
of antigen presentation cell remains largely a mystery. One of
research area in this group is focused on the process for loading of
peptides onto peptide-receptive MHC class I molecules and mechanism
for release of peptide loaded class I to present to antigen
presentation cells (APC). Killer Cell therapy based on MHC class
I-receptor interaction Cytotoxic T lymphocytes (CTLs) can
recognize and destroy infected or mutated cells. This process is
initiated by interaction between T cell receptors (TCR) and class I
MHC molecules associated with peptides. The therapeutic efficacy of
adoptively transferred CTLs has been demonstrated in both murine
tumour models and in recent clinical trials. However, adoptive
transfer of CTLs has limitation due to the difficulty to generate
sufficient numbers of CTLs in vitro and subject to the control of
the regulatory T cells. To circumvent the problem we are using two
strategies to redirected killer cells for targeting tumour and
incurable infectious diseases . One is to link MHC class I
restricted TCR alpha and beta subunits to zeta subunit of CD3 complex
and then transduce the engineered TCR into T cells. The second
strategy is to screen TCR like antibodies specific to the peptide in
the complex with HAL-A2 molecules using phage display technology and
use TCR like antibodies to re-direct T or NK cells to kill tumours.
We have developed a loxp/CRE based lentivirus system and are using the
system to deliver TCR receptors and TCR-like single domain
antibodies into killer cells for re-directed targeting tumour and
infected cells.

Selected Publications
1, B Flutter, Fu HM, Wedderburn L and B Gao
An extra molecule in addition to human tapasin is required for surface
expression of beta2m linked HLA-B4402 on murine cell.
Mol Immunol. 44(14):3528-36., 2007

2, SZ Xu, F Zeng, M Lei, J Li, B Gao, C Xiong, A Sivaprasadarao and DJ
Beech Generation of functional ion channel tools by E3-targeting
Nat Biotechnology 23:1289 - 1293 ,2005
3, Gao B, Williams A, Sewell A, Elliott T. Generation of a functional,
soluble Tapasin protein from an alternatively spliced mRNA
Genes &
Immunity 5:101-108, 2004

4, B Gao, Adhikari R, Howarth M, Nakamura K, Gold MC, Hill AB, Knee R,
Michalak M, Elliott T. Assembly and antigen-presenting function of
MHC
class I molecules in cells lacking the ER chaperone calreticulin.
Immunity 16(1):99-109, 2002

5, Golgher D, Korangy F, Gao B, Gorski K, Jaffee E, Edidin M, Pardoll
DM,
Elliott T. An immunodominant MHC class II-restricted tumor antigen
is
conformation dependent and binds to the endoplasmic reticulum
chaperone, calreticulin.
J Immunol 167(1):147-55, 2001

6, B Gao and MP Esnouf: Elucidation of the core residues of an epitope
using membrane-based combinatorial peptide libraries.
J Biol Chem 271:24634-8, 1996

7, B Gao and Esnouf MP: Multiple interactive residues of recognition:
elucidation of discontinuous epitopes with linear peptides.
J Immunol 157:183-8, 1996

Laboratoray Staff
Changzhen Liu, PhD, Assistant Professor
Rongzhi Liu, PhD, Assistant Professor
Hua Tao, Centre Secretary

Postgraduates
Jie Ding 2006
Kevin Zhu 2006
Lei Wang 2006
Shu Zhou 2006

Wei Wang 2007
Huamin Han 2007
Wen He 2007
Lifei Wang 2007
Yunfeng Zhao 2007
Mingsheng Qu 2007