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E u r o S c i C o n c o n f e r e n c e o n

Protein, Proteomics and

Computational Biology

Biochemistry & Molecular Biology Journal

ISSN: 2471-8084

D e c e m b e r 0 6 - 0 7 , 2 0 1 8

Am s t e r d a m , N e t h e r l a n d s

Proteomics and Computational Biology 2018

Page 17

N

atural Killer T (NKT) cells are a unique T cell population characterized by

features of both the innate and adaptive immune response. Two main classes

of NKT cells (Type I and II) exist that express different antigen receptors (TCRs)

and respond to different glycolipids presented by the shared antigen-presenting

molecule CD1d. Type I NKT cells respond rapidly to the prototypical antigen

-galactosylceramide (-GalCer) and can secrete both pro- and anti-inflammatory

cytokines, while Type II NKT cells recognize the self-glycolipid sulfatide and are

thought to be controlling autoimmunity. The cytokine profile of Type I NKT cells

can be altered using modified synthetic glycolipids to produce the cytokine

response of choice. Through biophysical TCR binding affinity measurements,

as well as crystallographic studies of how the TCR engages different CD1d-

presented glycolipids, we and others have identified the structural basis of

glycolipid recognition by NKT cells. The TCR of Type I NKT cells binds to CD1d

with a conserved footprint, while inducing structural changes in both CD1d and

the glycolipid antigens. This conserved TCR binding mode allows for the design

of glycolipid antigens, predominantly analogs of -GalCer in an attempt to obtain

glycolipids that elicit a particular cytokine profile. We are especially interested

in identifying novel antigens that elicit pro-inflammatory cytokines, since they

have great potential as vaccine adjuvants. I will present our ongoing work on

characterizing novel CD1d-restricted antigens, which led us to a surprising

discovery.

Biography

Prof. Zajonc obtained his Ph.D. in Biology from the Friedrich

Alexander University in Erlangen, Germany in 2001, working on

fatty acid elongation and sphingolipid metabolism in yeast. For

his postdoctoral work, he joined the laboratory of Ian A. Wilson

at the Scripps Research Institute in La Jolla, California, where

he worked on the structural basis of glycolipid presentation

by the CD1 family. At that time, he made seminal findings

of how glycolipids can be recognized by T cells. In 2006, he

started his own lab at the La Jolla Institute for Immunology,

where he continued to work on microbial antigen recognition

by T cells, antibody recognition of viral antigens, as well as viral

interferencewith immune recognition. He has published over 90

peer-review papers in top tier journals including Science, Nature

Immunology, Journal of Experimental Medicine, Immunity and

PNAS.

dzajonc@liai.org

Modulating immune responses with

designed glycolipid antigens that

target Natural Killer T cells using a

structural-functional approach

Zajonc

Friedrich Alexander University (Erlangen, Germany)

Zajonc, Biochem Mol biol J Volume:4

DOI: 10.21767/2471-8084-C5-019